Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies
Open accessAbstract
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by the progressive loss of cholinergic neurons, leading to the onset of severe behavioral, motor and cognitive impairments. It is a pressing public health problem with no effective treatment. Existing therapies only provide symptomatic relief without being able to prevent, stop or reverse the pathologic process. While the molecular basis underlying this multifactorial neurodegenerative disorder remains a significant challenge, mitochondrial dysfunction appears to be a critical factor in the pathogenesis of this disease. It is therefore important to target mitochondrial dysfunction in the prodromal phase of AD to slow or prevent the neurodegenerative process and restore neuronal function. In this review, we discuss mechanisms of action and translational potential of current mitochondrial and bioenergetic therapeutics for AD including: mitochondrial enhancers to potentiate energy production; antioxidants to scavenge reactive oxygen species and reduce oxidative damage; glucose metabolism and substrate supply; and candidates that target apoptotic and mitophagy pathways to remove damaged mitochondria. While mitochondrial therapeutic strategies have shown promise at the preclinical stage, there has been little progress in clinical trials thus far.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Decrease in Δψm has been observed in several in vitro and in vivo AD models.
“A decrease in Δψm (or mitochondrial depolarization) has been observed in several in vitro and in vivo AD models [65,66]”
From Apoe4 and Alzheimer’s Disease Pathogenesis—Mitochondrial Deregulation and Targeted Therapeutic Strategies (2023) · cites this paper as [65]
The Mitochondrial Membrane Potential section (page unavailable) reports decreased Δψm in AD animal models and human cortical neurons studied ex vivo. This supports the animal-model finding, but the paper describes the neuronal evidence as ex vivo, not as a finding in several in vitro AD models. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMitochondrial dysfunction is heavily implicated in the ageing process and the pathogenesis of age-related diseases such as Alzheimer's disease.
“Mitochondrial dysfunction is heavily implicated in the ageing process and the pathogenesis of age-related diseases such as Alzheimer's disease (AD) [16].”
From Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin (2017) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
2 retracted
Safdar, A., Little, J. P., Stokl, A., Hettinga, B. P., Akhtar, M., & Tarnopolsky, M. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.211466 · Cited by 309 · see citing works
RetractedLokireddy, S., Wijesoma, I. W., Teng, S., Bonala, S., Gluckman, P. D., McFarlane, C., Sharma, M., & Kambadur, R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.005 · Cited by 154 · see citing works
RetractedRepertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Free radicals and antioxidants in normal physiological functions and human disease
Valko, M., Leibfritz, D., Moncol, J., Cronin, M. T. D., Mazur, M., & Telser, J. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.07.001 · Cited by 14,269 · see citing works
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227 · see citing works
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358 · see citing works
Cui, C., Cui, J., Jin, F., Cui, Y., Li, R., Jiang, X., Tian, Y., Wang, R. C., Jiang, P., & Gao, J. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479571 · Cited by 5,214 · see citing works
Pankiv, S., Clausen, T. H., Lamark, T., Brech, A., Bruun, J.-A., Outzen, H., Øvervatn, A., Bjørkøy, G., & Johansen, T. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702824200 · Cited by 4,578 · see citing works
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · see citing works
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674 · see citing works
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630 · see citing works
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in <i>PINK1</i>
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481 · see citing works
Youle, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273 · see citing works
Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
Twig, G., Elorza, A., Molina, A. J. A., Mohamed, H., Wikstrom, J. D., Walzer, G., Stiles, L., Haigh, S. E., Katz, S., Las, G., et al. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601963 · Cited by 3,082 · see citing works
The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923 · see citing works
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835 · see citing works
Kenyon, C. J. (2010) · Nature · doi:10.1038/nature08980 · Cited by 2,739 · see citing works
Physiological Roles of Mitochondrial Reactive Oxygen Species
Sena, L. A., & Chandel, N. S. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.09.025 · Cited by 2,632 · see citing works
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton, D. J., Gratton, J., McCabe, T. J. D., Fontana, J. T., Fujio, Y., Walsh, K., Franke, T. F., Papapetropoulos, A., & Sessa, W. C. (1999) · Nature · doi:10.1038/21218 · Cited by 2,612 · see citing works
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.22.3499 · Cited by 2,130 · see citing works
Korshunov, S. S., Skulachev, V. P., & Starkov, A. A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01159-9 · Cited by 1,727 · see citing works
Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells
Liu, L., Feng, D., Chen, G., Chen, M., Zheng, Q., Song, P., Ma, Q., Zhu, C., Wang, R., Qi, W., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2422 · Cited by 1,689 · see citing works
Transcriptional paradigms in mammalian mitochondrial biogenesis and function
Scarpulla, R. C. (2008) · Physiological Reviews · doi:10.1152/physrev.00025.2007 · Cited by 1,666 · see citing works
AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function
Hardie, D. G. (2011) · Genes & Development · doi:10.1101/gad.17420111 · Cited by 1,638 · see citing works
PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L. A., Kim, J., May, J., Tocilescu, M. A., Liu, W., Ko, H. S., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911187107 · Cited by 1,616 · see citing works
Antioxidants prevent health-promoting effects of physical exercise in humans
Ristow, M., Zarse, K., Oberbach, A., Klöting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., & Blüher, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903485106 · Cited by 1,582 · see citing works
Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress
Kops, G. J. P. L., Dansen, T. B., Polderman, P. E., Saarloos, I., Wirtz, K. W. A., Coffer, P. J., Huang, T.-T., Bos, J. L., Medema, R. H., & Burgering, B. M. T. (2002) · Nature · doi:10.1038/nature01036 · Cited by 1,580 · see citing works
Selective degradation of mitochondria by mitophagy
Kim, I., Rodriguez-Enriquez, S., & Lemasters, J. J. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.034 · Cited by 1,558 · see citing works
A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy
Lee, I. H., Cao, L., Mostoslavsky, R., Lombard, D. B., Liu, J., Bruns, N. E., Tsokos, M., Alt, F. W., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712145105 · Cited by 1,473 · see citing works
Jain, A., Lamark, T., Sjøttem, E., Bowitz Larsen, K., Atesoh Awuh, J., Øvervatn, A., McMahon, M., Hayes, J. D., & Johansen, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.118976 · Cited by 1,472 · see citing works
Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., Bannai, S., & Yamamoto, M. P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.16023 · Cited by 1,460 · see citing works
Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex Assembly
Rubinfeld, B., Albert, I., Porfiri, E., Fiol, C. J., Munemitsu, S. M., & Polakis, P. G. (1996) · Science · doi:10.1126/science.272.5264.1023 · Cited by 1,420 · see citing works
Targeting mitochondria metabolism for cancer therapy
Weinberg, S. E., & Chandel, N. S. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1712 · Cited by 1,385 · see citing works
Superoxide activates mitochondrial uncoupling proteins
Echtay, K. S., Roussel, D., St-Pierre, J., Jekabsons, M. B., Cadenas, S., Stuart, J. A., Harper, J. A., Roebuck, S. J., Morrison, A., Pickering, S., et al. (2002) · Nature · doi:10.1038/415096a · Cited by 1,382 · see citing works
Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL
Jin, S. M., Lazarou, M., Wang, C., Kane, L. A., Narendra, D. P., & Youle, R. J. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201008084 · Cited by 1,375 · see citing works
Mitochondrial abnormalities in Alzheimer's disease
Hirai, K., Aliev, G., Nunomura, A., Fujioka, H., Russell, R. L., Atwood, C. S., Johnson, A. B., Kress, Y., Vinters, H. V., Tabaton, M., et al. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-09-03017.2001 · Cited by 1,367 · see citing works
Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics
Martinou, J., & Youle, R. J. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.06.017 · Cited by 1,366 · see citing works
Nix is a selective autophagy receptor for mitochondrial clearance
Novak, I., Kirkin, V., McEwan, D. G., Zhang, J., Wild, P., Rozenknop, A., Rogov, V., Löhr, F., Popovic, D., Occhipinti, A., et al. (2010) · The EMBO Reports · doi:10.1038/embor.2009.256 · Cited by 1,309 · see citing works
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303 · see citing works
Regulation of autophagy by ROS: physiology and pathology
Scherz-Shouval, R., & Elazar, Z. (2011) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.07.007 · Cited by 1,263 · see citing works
Transcriptional regulatory circuits controlling mitochondrial biogenesis and function
Kelly, D. P., & Scarpulla, R. C. (2004) · Genes & Development · doi:10.1101/gad.1177604 · Cited by 1,243 · see citing works
Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide
Nisoli, E., Clementi, E., Paolucci, C., Cozzi, V., Tonello, C., Sciorati, C., Bracale, R., Valerio, A., Francolini, M., Moncada, S., et al. (2003) · Science · doi:10.1126/science.1079368 · Cited by 1,243 · see citing works
Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M., & Ristow, M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.011 · Cited by 1,209 · see citing works
Cassidy-Stone, A., Chipuk, J. E., Ingerman, E., Song, C., Yoo, C., Kuwana, T., Kurth, M. J., Shaw, J. T., Hinshaw, J. E., Green, D. R., et al. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.11.019 · Cited by 1,200 · see citing works
PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility
Wang, X., Winter, D., Ashrafi, G., Schlehe, J. S., Wong, Y. L., Selkoe, D. J., Rice, S. E., Steen, J. A. J., LaVoie, M. J., & Schwarz, T. L. (2011) · Cell · doi:10.1016/j.cell.2011.10.018 · Cited by 1,161 · see citing works
Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS
Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., Falcone, S., Valerio, A., Cantoni, O., Clementi, E., et al. (2005) · Science · doi:10.1126/science.1117728 · Cited by 1,107 · see citing works
Manczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., & Reddy, P. H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl066 · Cited by 1,104 · see citing works
S-Nitrosylation of Drp1 Mediates β-Amyloid-Related Mitochondrial Fission and Neuronal Injury
Cho, D.-H., Nakamura, T., Fang, J., Cieplak, P., Godzik, A., Gu, Z., & Lipton, S. A. (2009) · Science · doi:10.1126/science.1171091 · Cited by 1,092 · see citing works
The Cell Non-Autonomous Nature of Electron Transport Chain-Mediated Longevity
Durieux, J., Wolff, S., & Dillin, A. (2011) · Cell · doi:10.1016/j.cell.2010.12.016 · Cited by 1,059 · see citing works
Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036 · see citing works
Mitophagy: mechanisms, pathophysiological roles, and analysis
Ding, W.-X., & Yin, X.-M. (2012) · bchm · doi:10.1515/hsz-2012-0119 · Cited by 1,032 · see citing works
Juhaszova, M., Zorov, D. B., Kim, S.-H., Pepe, S., Fu, Q., Fishbein, K. W., Ziman, B. D., Wang, S., Kirsti Ytrehus, B., Antos, C. L., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19906 · Cited by 1,029 · see citing works
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011 · see citing works
Adiponectin Stimulates Production of Nitric Oxide in Vascular Endothelial Cells
Chen, H., Montagnani, M., Funahashi, T., Shimomura, I., & Quon, M. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307878200 · Cited by 993 · see citing works
Inhibiting Mitochondrial Fission Protects the Heart Against Ischemia/Reperfusion Injury
Ong, S.-B., Subrayan, S., Lim, S. Y., Yellon, D. M., Davidson, S. M., & Hausenloy, D. J. (2010) · Circulation · doi:10.1161/circulationaha.109.906610 · Cited by 986 · see citing works
PARIS (ZNF746) Repression of PGC-1α Contributes to Neurodegeneration in Parkinson's Disease
Shin, J.-H., Ko, H. S., Kang, H., Lee, Y., Lee, Y.-I., Pletinkova, O., Troconso, J. C., Dawson, V. L., & Dawson, T. M. (2011) · Cell · doi:10.1016/j.cell.2011.02.010 · Cited by 953 · see citing works
Uncoupling: new approaches to an old problem of bioenergetics
Skulachev, V. P. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(97)00091-1 · Cited by 893 · see citing works
Maurer, U., Charvet, C., Wagman, A. S., Dejardin, E., & Green, D. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.009 · Cited by 881 · see citing works
Gomez-Cabrera, M.-C., Domenech, E., Romagnoli, M., Arduini, A., Borras, C., Pallardo, F. V., Sastre, J., & Viña, J. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.1.142 · Cited by 844 · see citing works
Wang, X., Su, B., Siedlak, S. L., Moreira, P. I., Fujioka, H., Wang, Y., Casadesus, G., & Zhu, X. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804871105 · Cited by 835 · see citing works
Mańczak, M., Calkins, M. J., & Reddy, P. H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr139 · Cited by 830 · see citing works
The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP
Ricquier, D., & Bouillaud, F. (2000) · Biochemical Journal · doi:10.1042/bj3450161 · Cited by 806 · see citing works
Mitochondrial Dysfunction in Atherosclerosis
Madamanchi, N. R., & Runge, M. S. (2007) · Circulation Research · doi:10.1161/01.res.0000258450.44413.96 · Cited by 794 · see citing works
Yeh, E., Cunningham, M., Arnold, H., Chasse, D., Monteith, T., Ivaldi, G., Hahn, W. C., Stukenberg, P. T., Shenolikar, S., Uchida, T., et al. (2004) · Nature Cell Biology · doi:10.1038/ncb1110 · Cited by 791 · see citing works
Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790 · see citing works
Ristow, M., & Zarse, K. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.014 · Cited by 789 · see citing works
Narendra, D. P., Kane, L. A., Hauser, D. N., Fearnley, I. M., & Youle, R. J. (2010) · Autophagy · doi:10.4161/auto.6.8.13426 · Cited by 789 · see citing works
Sohal, R. S., Ku, H.-H., Agarwal, S., Forster, M. J., & Lal, H. (1994) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(94)90104-x · Cited by 788 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · cited 2× · see citing works
“A role for dysfunctional mitochondria in AD pathogenesis has been postulated [1-3].”
BackgroundSelf-citationHDAC6 controls autophagosome maturation essential for ubiquitin‐selective quality‐control autophagy
Lee, J., Koga, H., Kawaguchi, Y., Tang, W., Wong, E., Gao, Y., Pandey, U. B., Kaushik, S., Tresse, E., Lu, J., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2009.405 · Cited by 756 · see citing works
Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models
Brooks, C., Wei, Q., Cho, S.-G., & Dong, Z. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37829 · Cited by 735 · see citing works
Simonsen, A., Cumming, R. C., Brech, A., Isakson, P., Schubert, D. R., & Finley, K. D. (2008) · Autophagy · doi:10.4161/auto.5269 · Cited by 716 · see citing works
Gleyzer, N., Vercauteren, K., & Scarpulla, R. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.4.1354-1366.2005 · Cited by 711 · see citing works
Mitochondrial Electron Transport Is a Key Determinant of Life Span in Caenorhabditis elegans
Feng, J., Bussière, F., & Hekimi, S. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00071-5 · Cited by 675 · see citing works
Little, J. P., Safdar, A., Wilkin, G. P., Tarnopolsky, M. A., & Gibala, M. J. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2009.181743 · Cited by 672 · see citing works
Mitochondrial Complex III ROS Regulate Adipocyte Differentiation
Tormos, K. V., Ansó, E., Hamanaka, R. B., Eisenbart, J. D., Joseph, J., Kalyanaraman, B., & Chandel, N. S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.007 · Cited by 662 · see citing works
MiD49 and MiD51, new components of the mitochondrial fission machinery
Palmer, C. S., Osellame, L. D., Laine, D., Koutsopoulos, O. S., Frazier, A. E., & Ryan, M. T. (2011) · The EMBO Reports · doi:10.1038/embor.2011.54 · Cited by 649 · see citing works
Mitochondrial fusion, fission and autophagy as a quality control axis: The bioenergetic view
Twig, G., Hyde, B. B., & Shirihai, O. S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.05.001 · Cited by 646 · see citing works
Calkins, M. J., Manczak, M., Mao, P., Shirendeb, U., & Reddy, P. H. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr381 · Cited by 646 · see citing works
Short, K. R., Vittone, J. L., Bigelow, M. L., Proctor, D. N., Rizza, R. A., Coenen-Schimke, J. M., & Nair, K. S. (2003) · Diabetes · doi:10.2337/diabetes.52.8.1888 · Cited by 631 · see citing works
Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Votyakova, T. V., & Reynolds, I. J. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00548.x · Cited by 601 · see citing works
Abramov, A. Y., Canevari, L., & Duchen, M. R. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4042-03.2004 · Cited by 587 · see citing works
FOXOs, cancer and regulation of apoptosis
Fu, Z., & Tindall, D. J. (2008) · Oncogene · doi:10.1038/onc.2008.24 · Cited by 584 · see citing works
Mitochondrial-nuclear communications
Ryan, M. T., & Hoogenraad, N. J. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052305.091720 · Cited by 575 · see citing works
Is Akt the “Warburg kinase”?—Akt-energy metabolism interactions and oncogenesis
Robey, R. B., & Hay, N. (2008) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2008.11.010 · Cited by 543 · see citing works
Cancer Chemoprevention Mechanisms Mediated Through the Keap1–Nrf2 Pathway
Hayes, J. D., McMahon, M. J., Chowdhry, S., & Dinkova‐Kostova, A. T. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3221 · Cited by 540 · see citing works
Impaired Mitochondrial Biogenesis Contributes to Mitochondrial Dysfunction in Alzheimer's Disease
Sheng, B., Wang, X.-L., Su, B., Lee, H.-G., Casadesus, G., Perry, G., & Zhu, X.-W. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07581.x · Cited by 538 · see citing works
Lee, J., Nagano, Y., Taylor, J. P., Lim, K. L., & Yao, T. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201001039 · Cited by 517 · see citing works
Mitochondrial biogenesis by NO yields functionally active mitochondria in mammals
Nisoli, E., Falcone, S., Tonello, C., Cozzi, V., Palomba, L., Fiorani, M., Pisconti, A., Brunelli, S., Cardile, A., Francolini, M., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405432101 · Cited by 495 · see citing works
Deshpande, A. M., Mina, E. W., Glabe, C. G., & Busciglio, J. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1189-06.2006 · Cited by 490 · see citing works
A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients
Maurer, I. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00112-3 · Cited by 475 · see citing works
Pecqueur, C., Alves‐Guerra, M., Gelly, C., Lévi-Meyrueis, C., Couplan, E., Collins, S., Ricquier, D., Bouillaud, F., & Miroux, B. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006938200 · Cited by 474 · see citing works
Hauptmann, S., Scherping, I., Dröse, S., Brandt, U., Schulz, K. L., Jendrach, M., Leuner, K., Eckert, A., & Müller, W. E. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.12.005 · Cited by 469 · see citing works
Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation
Skulachev, V. P. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80658-p · Cited by 467 · see citing works
Mitochondrial H + Leak and ROS Generation: An Odd Couple
Brookes, P. S. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.10.016 · Cited by 447 · see citing works
Keller, J. N., Pang, Z., Geddes, J. W., Begley, J. G., Germeyer, A., Waeg, G., & Mattson, M. P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010273.x · Cited by 439 · see citing works
Energy intake and exercise as determinants of brain health and vulnerability to injury and disease
Mattson, M. P. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.012 · Cited by 434 · see citing works
Membrane Remodeling Induced by the Dynamin-Related Protein Drp1 Stimulates Bax Oligomerization
Montessuit, S., Somasekharan, S. P., Terrones, O., Lucken‐Ardjomande, S., Herzig, S., Schwarzenbacher, R., Manstein, D. J., Bossy‐Wetzel, E., Basáñez, G., Meda, P., et al. (2010) · Cell · doi:10.1016/j.cell.2010.08.017 · Cited by 422 · see citing works
Extension of Drosophila Life Span by RNAi of the Mitochondrial Respiratory Chain
Copeland, J. M., Cho, J., Lo, T., Hur, J. H., Bahadorani, S., Arabyan, T., Rabie, J., Soh, J., & Walker, D. W. (2009) · Current Biology · doi:10.1016/j.cub.2009.08.016 · Cited by 409 · see citing works
Effects of exercise on mitochondrial content and function in aging human skeletal muscle
Menshikova, E. V., Ritov, V. B., Fairfull, L., Ferrell, R. E., Kelley, D. E., & Goodpaster, B. H. (2006) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/61.6.534 · Cited by 398 · see citing works
Reddy, P. H., Tripathi, R., Troung, Q., Tirumala, K., Reddy, T. P., Anekonda, V., Shirendeb, U. P., Calkins, M. J., Reddy, A. P., Mao, P., et al. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.011 · Cited by 394 · see citing works
PGC-1α Expression Decreases in the Alzheimer Disease Brain as a Function of Dementia
Qin, W., Haroutunian, V. H., Katsel, P., Cardozo, C. P., Ho, L., Buxbaum, J. D., & Pasinetti, G. M. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.588 · Cited by 381 · see citing works
RALA and RALBP1 regulate mitochondrial fission at mitosis
Kashatus, D. F., Lim, K.-H., Brady, D. C., Pershing, N. L. K., Cox, A. D., & Counter, C. M. (2011) · Nature Cell Biology · doi:10.1038/ncb2310 · Cited by 380 · see citing works
Redox-optimized ROS balance: A unifying hypothesis
Aon, M. A., Cortassa, S. C., & O'Rourke, B. P. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.016 · Cited by 376 · see citing works
Targeting Mitochondrial Dysfunction: Role for PINK1 and Parkin in Mitochondrial Quality Control
Narendra, D. P., & Youle, R. J. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3799 · Cited by 367 · see citing works
Mitochondrial dysfunction in ataxia-telangiectasia
Valentin-Vega, Y. A., MacLean, K. H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F. C., Cleveland, J. L., Green, D. R., & Kastan, M. B. (2012) · Blood · doi:10.1182/blood-2011-08-373639 · Cited by 365 · see citing works
Exercise training increases mitochondrial biogenesis in the brain
Steiner, J. L., Murphy, E. A., McClellan, J. L., Carmichael, M. D., & Davis, J. M. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00343.2011 · Cited by 357 · see citing works
Abnormalities of mitochondrial enzymes in Alzheimer disease
Gibson, G. E., Sheu, K.-F. R., & Blass, J. P. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050099 · Cited by 345 · see citing works
Increased longevity and refractoriness to Ca2+-dependent neurodegeneration in Surf1 knockout mice
Dell'Agnello, C., Leo, S., Agostino, A., Szabadkai, G., Tiveron, C., Zulian, A., Prelle, A., Roubertoux, P., Rizzuto, R., & Zeviani, M. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddl477 · Cited by 308 · see citing works
Murphy, M. P., Echtay, K. S., Blaikie, F. H., Asin-Cayuela, J., Cochemé, H. M., Green, K., Buckingham, J. A., Taylor, E. R., Hurrell, F., Hughes, G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308529200 · Cited by 304 · see citing works
Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling
Miwa, S., & Brand, M. D. (2003) · Biochemical Society Transactions · doi:10.1042/bst0311300 · Cited by 288 · see citing works
Prohibitin and mitochondrial biology
Artal‐Sanz, M., & Tavernarakis, N. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.04.004 · Cited by 285 · see citing works
Liu, X., & Hajnóczky, G. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.13 · Cited by 285 · see citing works
Amyloid beta, mitochondrial structural and functional dynamics in Alzheimer's disease
Reddy, P. H. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.03.042 · Cited by 264 · see citing works
Amyloid β-peptide induces apoptosis-related events in synapses and dendrites
Mattson, M. P., Partin, J. V., & Begley, J. G. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00763-x · Cited by 260 · see citing works
Mitochondrial biogenesis in exercise and in ageing☆
Viña, J., Gómez‐Cabrera, M. C., Borrás, C., Froio, T., Sanchis‐Gomar, F., Martinez-Bello, V. E., & Pallardó, F. V. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.06.006 · Cited by 251 · see citing works
Fukui, H., & Moraes, C. T. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.008 · Cited by 248 · see citing works
BRENNAN, J., SOUTHWORTH, R., MEDINA, R., DAVIDSON, S., DUCHEN, M., & SHATTOCK, M. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.07.019 · Cited by 242 · see citing works
Signaling pathways in mitochondrial dysfunction and aging
Mammucari, C., & Rizzuto, R. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.07.003 · Cited by 239 · see citing works
Caloric restriction in humans: Potential pitfalls and health concerns
Dirks, A. J., & Leeuwenburgh, C. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.09.001 · Cited by 239 · see citing works
Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism
Mosconi, L., Brys, M., Switalski, R., Mistur, R., Glodzik, L., Pirraglia, E., Tsui, W., De Santi, S., & de Leon, M. J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705036104 · Cited by 237 · see citing works
The SirT3 Divining Rod Points to Oxidative Stress
Bell, E. L., & Guarente, L. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.05.008 · Cited by 232 · see citing works
Mitochondrial Medicine for Aging and Neurodegenerative Diseases
Reddy, P. H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8044-z · Cited by 230 · see citing works
Rapidly Increased Neuronal Mitochondrial Biogenesis After Hypoxic-Ischemic Brain Injury
Yin, W., Signore, A. P., Iwai, M., Cao, G., Gao, Y., & Chen, J. (2008) · Stroke · doi:10.1161/strokeaha.108.520114 · Cited by 229 · see citing works
Metabolism of activated T lymphocytes
Maciolek, J. A., Pasternak, J. A., & Wilson, H. L. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.01.006 · Cited by 224 · see citing works
Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics
Alto, N. M., Soderling, J. A., & Scott, J. D. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200204081 · Cited by 222 · see citing works
Nakamura, T., & Lipton, S. A. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.65 · Cited by 222 · see citing works
Effects of overexpression of Huntingtin proteins on mitochondrial integrity
Wang, H., Lim, P. J., Karbowski, M., & Monteiro, M. J. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn404 · Cited by 222 · see citing works
Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals
Lefevre, M., Redman, L. M., Heilbronn, L. K., Smith, J. V., Martin, C. K., Rood, J. C., Greenway, F. L., Williamson, D. A., Smith, S. R., & Ravussin, E. (2009) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.05.036 · Cited by 217 · see citing works
Bcl-x L induces Drp1-dependent synapse formation in cultured hippocampal neurons
Li, H., Chen, Y., Jones, A., Sanger, R. H., Collis, L. P., Flannery, R. J., McNay, E. C., Yu, T., Schwarzenbacher, R., Bossy, B., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711647105 · Cited by 216 · see citing works
Bennett, C. F., Wende, H. V., Simko, M., Klum, S., Barfield, S., Choi, H., Pineda, V. V., & Kaeberlein, M. R. (2014) · Nature Communications · doi:10.1038/ncomms4483 · Cited by 215 · see citing works
A fundamental system of cellular energy homeostasis regulated by PGC-1α
Rohas, L. M., St‐Pierre, J., Uldry, M., Jäger, S., Handschin, C., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702683104 · Cited by 210 · see citing works
Regulation of cytochrome c oxidase activity by c-Src in osteoclasts
Miyazaki, T., Neff, L., Tanaka, S., et al. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200209098 · Cited by 210 · see citing works
Mitochondrial Dysfunction: Different Routes to Alzheimer’s Disease Therapy
Picone, P., Nuzzo, D., Caruana, L., Scafidi, V., & Carlo, M. D. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/780179 · Cited by 208 · see citing works
Cui, M., Tang, X., Christian, W. V., Yoon, Y., & Tieu, K. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.066662 · Cited by 205 · see citing works
Regulation of mitophagy by the Gp78 E3 ubiquitin ligase
Fu, M., St-Pierre, P., Shankar, J., Wang, P. T. C., Joshi, B., & Nabi, I. R. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-08-0607 · Cited by 204 · see citing works
Reynolds, L. M., Taylor, J. R., Ding, J., Lohman, K., Johnson, C. W., Siscovick, D. S., Burke, G. L., Post, W. S., Shea, S., Jacobs, D. R., et al. (2014) · Nature Communications · doi:10.1038/ncomms6366 · Cited by 201 · see citing works
Das, S., Wong, R. P., Rajapakse, N. C., Murphy, E., & Steenbergen, C. (2008) · Circulation Research · doi:10.1161/circresaha.108.178970 · Cited by 197 · see citing works
Fatty acid cycling mechanism and mitochondrial uncoupling proteins
Ježek, P., Engstová, H., Žáčková, M., Vercesi, A. E., Costa, A. D. T., Arruda, P., & Garlid, K. D. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00084-x · Cited by 196 · see citing works
Dominy, J. E., Lee, Y., Gerhart‐Hines, Z., & Puigserver, P. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.11.023 · Cited by 192 · see citing works
Emerging Role for Members of the Bcl-2 Family in Mitochondrial Morphogenesis
Autret, A., & Martin, S. J. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.10.011 · Cited by 190 · see citing works
Regulation of neuron mitochondrial biogenesis and relevance to brain health
Onyango, I. G., Lu, J., Rodova, M., Lezi, E., Crafter, A. B., & Swerdlow, R. H. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.07.014 · Cited by 188 · see citing works
Self-citationNutrition and neurodegeneration: epidemiological evidence and challenges for future research
Guyonnet, S., Secher, M., & Vellas, B. J. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12058 · Cited by 187 · see citing works
Mitochondrial alterations near amyloid plaques in an Alzheimer’s disease mouse model
Xie, H., Guan, J., Borrelli, L. A., Xu, J., Serrano-Pozo, A., & Bacskai, B. J. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1836-13.2013 · Cited by 185 · see citing works
Regulation of Late G1/S Phase Transition and APCCdh1by Reactive Oxygen Species
Havens, C. G., Ho, A. L., Yoshioka, N., & Dowdy, S. F. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00303-06 · Cited by 182 · see citing works
Neurodegeneration as a consequence of failed mitochondrial maintenance
Karbowski, M., & Neutzner, A. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0921-0 · Cited by 182 · see citing works
Mitochondrial superoxide and aging: uncoupling-protein activity and superoxide production
Brand, M. D., Buckingham, J. A., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Murphy, M. P., Pakay, J. L., Talbot, D. A., & Echtay, K. S. (2004) · Biochemical Society Symposia · doi:10.1042/bss0710203 · Cited by 182 · see citing works
Cheng, X., Siow, R. C. M., & Mann, G. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3283 · Cited by 181 · see citing works
Saresella, M., Calabrese, E., Marventano, I., Piancone, F., Gatti, A., Alberoni, M., Nemni, R., & Clerici, M. (2011) · Brain, behavior, and immunity · doi:10.1016/j.bbi.2010.12.004 · Cited by 181 · see citing works
Autophagy in the heart and liver during normal aging and calorie restriction
Wohlgemuth, S. E., Julian, D., Akin, D. E., Fried, J., Toscano, K., Leeuwenburgh, C., & Dunn, Jr. (2007) · Rejuvenation Research · doi:10.1089/rej.2006.0535 · Cited by 179 · see citing works
Targeting of protein kinase C delta to mitochondria in the oxidative stress response.
Majumder, P. K., Mishra, N. C., Sun, X., Bharti, A. K., Kharbanda, S. M., Saxena, S. P., & Kufe, D. W. (2001) · PubMed · Cited by 171 · see citing works
Signaling of Mitochondrial Biogenesis following Oxidant Injury
Rasbach, K. A., & Schnellmann, R. G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608009200 · Cited by 168 · see citing works
Acute endurance exercise increases the nuclear abundance of PGC-1α in trained human skeletal muscle
Little, J. P., Safdar, A., Cermak, N. M., Tarnopolsky, M. A., & Gibala, M. J. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00409.2009 · Cited by 163 · see citing works
Bossy, B., Petrilli, A. M., Klinglmayr, E., Chen, J., Lütz‐Meindl, U., Knott, A. B., Masliah, E., Schwarzenbacher, R., & Bossy‐Wetzel, E. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100552 · Cited by 162 · see citing works
Cellular signaling in the aging immune system
Fulop, T., Le Page, A., Fortin, C., Witkowski, J. M., Dupuis, G., & Larbi, A. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.007 · Cited by 158 · see citing works
On the immunological theory of aging
Fulop, T., Witkowski, J. M., Pawelec, G., Alan, C., & Larbi, A. (2014) · Interdisciplinary topics in gerontology and geriatrics · doi:10.1159/000358904 · Cited by 157 · see citing works
Mitochondrial AKAP121 Links cAMP and src Signaling to Oxidative Metabolism
Livigni, A., Scorziello, A., Agnese, S., Adornetto, A., Carlucci, A., Garbi, C., Castaldo, I., Annunziato, L., Avvedimento, E. V., & Feliciello, A. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-09-0827 · Cited by 154 · see citing works
PMI: A ΔΨm Independent Pharmacological Regulator of Mitophagy
East, D. A., Fagiani, F., Crosby, J., Georgakopoulos, N., Bertrand, H. C., Schaap, M., Fowkes, A., Wells, G., & Campanella, M. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.09.019 · Cited by 153 · see citing works
Increased Autophagic Degradation of Mitochondria in Alzheimer Disease
Moreira, P. I., Siedlak, S. L., Wang, X., Santos, M. S., Oliveira, C. R., Tabaton, M., Nunomura, A., Szweda, L. I., Aliev, G. M., Smith, M. A., et al. (2007) · Autophagy · doi:10.4161/auto.4872 · Cited by 150 · see citing works
Uncoupling Proteins 2 and 3 Function in Concert to Augment Tolerance to Cardiac Ischemia
McLeod, C. J., Aziz, A., Hoyt, R. F., McCoy, J. P., & Sack, M. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505258200 · Cited by 150 · see citing works
Hoerter, J. A., González‐Barroso, M. M., Couplan, E., Matéo, P., Gelly, C., Cassard, A., Diolez, P., & Bouillaud, F. (2004) · Circulation · doi:10.1161/01.cir.0000137824.30476.0e · Cited by 149 · see citing works
Carboxyatractylate inhibits the uncoupling effect of free fatty acids
Andreyev, A. Y., BONDAREVA, T. O., Dedukhova, V. I., MOKHOVA, E. N., Skulachev, V. P., & Волков, Н. И. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)81436-4 · Cited by 149 · see citing works
Mitochondrial Dysfunction Contributes to the Pathogenesis of Alzheimer’s Disease
Cabezas-Opazo, F., Vergara-Pulgar, K., Maria Jose Perez, J., Jara, C., Osorio‐Fuentealba, C., & Quintanilla, R. A. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/509654 · Cited by 148 · see citing works
Park, S. W., Keun-young Kim, A., Lindsey, J. D., Dai, Y. L., Heo, H., Nguyen, D. H., Ellisman, M. H., Weinreb, R. N., & Ju, W. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-5010 · Cited by 145 · see citing works
Cytochrome C Oxidase in Alzheimer's Disease Brain: Purification and Characterization
Parker, W. D., & Parks, J. K. (1995) · Neurology · doi:10.1212/wnl.45.3.482 · Cited by 142 · see citing works
Donati, A., Cavallini, G., Paradiso, C., Vittorini, S., Pollera, M., Gori, Z., & Bergamini, E. (2001) · The Journals of Gerontology Series A · doi:10.1093/gerona/56.9.b375 · Cited by 142 · see citing works
Petersen, A. J., Rimkus, S. A., & Wassarman, D. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110470109 · Cited by 139 · see citing works
The Role of Autophagy in Aging
Bergamini, E., Cavallini, G., Donati, A., & Gori, Z. (2007) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1396.020 · Cited by 136 · see citing works
Assessing mitochondria biogenesis
Medeiros, D. M. (2008) · Methods · doi:10.1016/j.ymeth.2008.09.026 · Cited by 135 · see citing works
Ghosh, S., Lertwattanarak, R., Lefort, N., Molina-Carrion, M., Joya-Galeana, J., Bowen, B. P., Garduno-Garcia, J. D. J., Abdul-Ghani, M., Richardson, A., DeFronzo, R. A., et al. (2011) · Diabetes · doi:10.2337/db11-0121 · Cited by 128 · see citing works
Ramsden, D. B., Ho, P. W., Ho, J. W.-M., Liu, H., So, D. H. ‐., Tse, H., Chan, K., & Ho, S. (2012) · Brain and Behavior · doi:10.1002/brb3.55 · Cited by 127 · see citing works
Mitochondrial Dysfunction—A Pharmacological Target in Alzheimer's Disease
Eckert, G. P., Renner, K., Eckert, S. H., Eckmann, J., Hagl, S., Abdel-Kader, R. M., Kurz, C., Leuner, K., & Muller, W. E. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8271-z · Cited by 126 · see citing works
Peroxynitrite and Brain Mitochondria: Evidence for Increased Proton Leak
Brookes, P. S., Land, J. M., Clark, J. B., & Heales, S. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052195.x · Cited by 125 · see citing works
Dysregulation of T-Cell Function in the Elderly
Fülöp, T., Larbi, A., Wikby, A., Mocchegiani, E., Hirokawa, K., & Pawelec, G. (2005) · Drugs & Aging · doi:10.2165/00002512-200522070-00005 · Cited by 122 · see citing works
Evidence for Physiological Down-regulation of Brain Oxidative Phosphorylation in Alzheimer's Disease
Chandrasekaran, K., Hatanpaa, K. J., Brady, D. R., & Rapoport, S. I. (1996) · Experimental Neurology · doi:10.1006/exnr.1996.0180 · Cited by 117 · see citing works
Energetic requirements and bioenergetic modulation of mitochondrial morphology and dynamics
Sauvanet, C., Duvezin‐Caubet, S., di Rago, J., & Rojo, M. (2009) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2009.12.006 · Cited by 114 · see citing works
Melov, S., Hinerfeld, D. A., Esposito, L., & Wallace, D. C. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.5.974 · Cited by 113 · see citing works
NAD+ as a Signaling Molecule Modulating MetabolismPreprint
Cantó, C., & Auwerx, J. H. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2012.76.010439 · Cited by 109 · see citing works
Kumar, S., Bharti, A. K., Mishra, N. C., Raina, D., Kharbanda, S. M., Saxena, S. P., & Kufe, D. W. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101414200 · Cited by 108 · see citing works
Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability
Horn, S. R. G.-V., Thomenius, M. J., Johnson, E. S., Freel, C. D., Wu, J. Q., Coloff, J. L., Yang, C., Tang, W., An, J., Ilkayeva, O., et al. (2011) · Molecular Biology of the Cell · doi:10.1091/mbc.e10-07-0567 · Cited by 101 · see citing works
Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle
Psilander, N., Frank, P., Flockhart, M., & Sahlin, K. (2013) · European Journal of Applied Physiology · doi:10.1007/s00421-012-2504-8 · Cited by 101 · see citing works
Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia and brain ischaemia
Carlucci, A., Adornetto, A., Scorziello, A., Viggiano, D., Foca, M., Cuomo, O., Annunziato, L., Gottesman, M. E., & Feliciello, A. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.33 · Cited by 98 · see citing works
Mitochondrial Dynamics in Disease
Chan, D. C. (2007) · New England Journal of Medicine · doi:10.1056/nejmp078040 · Cited by 94 · see citing works
Rashid, G., Bernheim, J., Green, J., et al. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm269 · Cited by 90 · see citing works
Cerqueira, F. M., Laurindo, F. R. M., & Kowaltowski, A. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018433 · Cited by 87 · see citing works
Mitochondrial quality control and neurological disease: an emerging connection
de Castro, I. P., Martins, L. M., & Tufi, R. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001456 · Cited by 87 · see citing works
Mitochondrial VDAC Can Be Phosphorylated by Cyclic AMP-Dependent Protein Kinase
Bera, A. K., Ghosh, S., & Das, S. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1491 · Cited by 82 · see citing works
Dual destructive and protective roles of adaptive immunity in neurodegenerative disorders
Anderson, K. M., Olson, K. E., Estes, K. A., Flanagan, K., Gendelman, H. E., & Mosley, R. L. (2014) · Translational Neurodegeneration · doi:10.1186/2047-9158-3-25 · Cited by 81 · see citing works
Bruni, F., Polosa, P. L., Gadaleta, M. N., Cantatore, P., & Roberti, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.044305 · Cited by 77 · see citing works
Calkins, M. J., Mańczak, M., & Reddy, P. (2012) · Pharmaceuticals · doi:10.3390/ph5101103 · Cited by 71 · see citing works
Src‐Tyrosine kinases are major agents in mitochondrial tyrosine phosphorylation
Tibaldi, E. V., Brunati, A. M., Massimino, M. L., Stringaro, A., Colone, M., Agostinelli, E., Arancia, G., & Toninello, A. (2008) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21670 · Cited by 70 · see citing works
Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis
Ohashi, S., Nishio, A., Nakamura, H., Kido, M., Ueno, S., Uza, N., Inoue, S., Kitamura, H., Kiriya, K., Asada, M., et al. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00425.2005 · Cited by 66 · see citing works
Martel, C., Allouche, M., Esposti, D. D., Fanelli, E., Boursier, C., Henry, C., Chopineau, J., Calamita, G., Kroemer, G., Lemoine, A., et al. (2012) · Hepatology · doi:10.1002/hep.25967 · Cited by 65 · see citing works
Bennett, C. F., & Kaeberlein, M. R. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.02.002 · Cited by 61 · see citing works
Hu, Z., Chen, J., Wei, Q., & Xia, Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802455200 · Cited by 59 · see citing works
Mocchegiani, E., Giacconi, R., Cipriano, C., Gasparini, N., Bernardini, G., Malavolta, M., Menegazzi, M., Cavalieri, E., Muzzioli, M., Ciampa, A. R., et al. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.01.014 · Cited by 54 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [30]Medeiros DM (2008). Assessing mitochondria biogenesis. Methods, 46: 288- 294 18929661
- [38]Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, et al (2001). Mitochondrial abnormalities in Alzheimer's disease. J Neurosci, 21: 3017- 3023 11312286 PMC6762571
Cited by
Sorted by citations
Song, T., Song, X., Zhu, C., Patrick, R., Skurla, M., Santangelo, I., Green, M., Harper, D., Ren, B., Forester, B. P., et al. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101503 · Cited by 346 · see citing works
Pires, M., & Rego, A. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010778 · Cited by 157 · see citing works
Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration
Jha, S. K., Jha, N. K., Kumar, D., Ambasta, R. K., & Kumar, P. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.06.015 · Cited by 122 · see citing works
New therapeutics beyond amyloid-β and tau for the treatment of Alzheimer’s disease
Zhang, F., Zhong, R.-J., Cheng, C., Li, S., & Le, W.-D. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00565-5 · Cited by 105 · see citing works
Glucocorticoid impairs mitochondrial quality control in neurons
Choi, G. E., & Han, H. J. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105301 · Cited by 95 · see citing works
Kamila, P., Kar, K., Chowdhury, S., Chakraborty, P., Dutta, R., S, S., Singh S, A., & Prajapati, B. G. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.05.005 · Cited by 90 · see citing works
Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin
Naidoo, K., & Birch-Machin, M. (2017) · Cosmetics · doi:10.3390/cosmetics4010004 · Cited by 83 · see citing works
Association of Aβ with ceramide-enriched astrosomes mediates Aβ neurotoxicity
Elsherbini, A., Kirov, A. S., Dinkins, M. B., Wang, G., Qin, H., Zhu, Z., Tripathi, P., Crivelli, S. M., & Bieberich, E. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00931-8 · Cited by 72 · see citing works
Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48 · see citing works
“The mitochondrial pathology in AD and PD is further exacerbated by impaired mitochondrial biogenesis, a mechanism that leads to the generation of additional mitochondria to meet greater energetic demands in cells, and mitophagy, which is a form of autophagy that mediates the degradation of malfunctional, ROS-overprodu…”
BackgroundAhmed, M., Malik, M., Teselink, J., Lanctôt, K. L., & Herrmann, N. (2019) · Drugs & Aging · doi:10.1007/s40266-019-00668-7 · Cited by 29 · see citing works
Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease?
Hindle, A., Singh, S. P., Pradeepkiran, J. A., Bose, C., Vijayan, M., Kshirsagar, S., Sawant, N. A., & Reddy, P. H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116098 · Cited by 14 · see citing works
- Authors
- Onyango, I. G., Dennis, J., & Khan, S. M.
- Affiliations
- Gencia (United States) (US)
- Corresponding author
- Onyango, Isaac G.
- ORCID
- Onyango, Isaac G.
- Venue
- Aging and Disease
- Publisher
- Aging and Disease
- Published
- 2016
- Volume
- 7
- Issue
- 2
- Pages
- 201
- ISSN
- 2152-5250 (ISSN-L)
- PMC
- PMC4809610
- OpenAlex
- W2321151839
- Cited by
- 260
- References
- 205
- Citations by year
- 2026: 13 · 2025: 24 · 2024: 16 · 2023: 16 · 2022: 22 · 2021: 35 · 2020: 30 · 2019: 32 · 2018: 40 · 2017: 19 · 2016: 12
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Aging and Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, mitochondrial dysfunction, bioenergetics, antioxidants, reactive oxygen species, glucose metabolism, substrate supply, apoptosis, mitophagy, neurodegeneration, cholinergic neurons, mitochondrial therapeutics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review