Pgc-1α overexpression Via local transfection attenuates mitophagy pathway in muscle disuse atrophy
Abstract
Loss of mitochondrial structural and functional integrity plays a critical role in the pathogenesis of muscle disuse atrophy. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) has been suggested to modulate autophagy-lysosome pathway (mitophagy) during muscle atrophy, but clear evidence is still lacking. In the current study, we tested the hypothesis that overexpression of PGC-1α via in vivo transfection would ameliorate mitophagy in mouse tibialis anterior muscle subjected to two weeks of immobilization (IM), followed by remobilization (RM). While mitochondrial biogenesis and antioxidant enzymes are decreased, all autophagic and mitophagic protein markers such as Beclin-1, Bnip3, PINK1, parkin, Mul1 and the LC3II/LC3I ratio were increased in IM-RM muscle together with activation of FoxO pathway. Overexpression of PGC-1α significantly increased mitochondrial DNA proliferation and oxidative enzyme activity, whereas it mitigated oxidative stress and mitochondrial ubiquination in IM-RM muscle. Protein contents of PINK1, parkin and Mul1 in mitochondria decreased by approximately 50% with PGC-1α treatment. Furthermore, PGC-1α overexpression suppressed FoxO1 and FoxO3 activation along with a decreased LC3II/LC3I ratio. Importantly, PGC-1α attenuated IM-RM-induced ubiquination and degradation of mitofusion protein Mfn2. Muscle apoptotic tendency, measured by Bax/Bcl2 ratio and caspase-3 activity, were elevated with IM-RM, but unaffected by PGC-1α. We conclude that overexpression of PGC-1α by in vivo transfection can inhibit activation of mitophagy pathway in the atrophying muscle caused by immobilization.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
PGC-1α overexpression reduces the expression of PINK1 and Parkin in muscle disuse atrophy.
“Besides, PGC-1α overexpression reduced the expression of PINK1 and Parkin in muscle disuse atrophy (98).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [98]
Overexpression of PGC-1α attenuates Pink1 levels in response to remobilization of muscle.
“overexpression of PGC-1α was reported to attenuate Pink1 levels in response to remobilization of muscle (67).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [67]
Cites
2 retracted
Wenz, T., Rossi, S. G., Rotundo, R. L., Spiegelman, B. M., & Moraes, C. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911570106 · Cited by 600 · 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
RetractedReactive oxygen species, cellular redox systems, and apoptosis
Circu, M. L., & Aw, T. Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.022 · Cited by 3,340 · 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
St-Pierre, J., Drori, S., Uldry, M., Silvaggi, J. M., Rhee, J., Jäger, S., Handschin, C., Zheng, K., Lin, J., Yang, W., et al. (2006) · Cell · doi:10.1016/j.cell.2006.09.024 · Cited by 2,233 · see citing works
FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.001 · Cited by 1,953 · see citing works
The mitochondrial membrane potential (Δψm) in apoptosis; an update
Ly, J. D., Grubb, D. R., & Lawen, A. (2003) · APOPTOSIS · doi:10.1023/a:1022945107762 · Cited by 1,599 · see citing works
Zhao, J., Brault, J. J., Schild, A., Cao, P., Sandri, M., Schiaffino, S., Lecker, S. H., & Goldberg, A. L. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.004 · Cited by 1,489 · see citing works
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438 · 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
Cellular and molecular mechanisms of muscle atrophy
Bonaldo, P., & Sandri, M. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.010389 · Cited by 1,284 · see citing works
Chen, H., Vermulst, M., Wang, Y. E., Chomyn, A., Prolla, T. A., McCaffery, J. M., & Chan, D. C. (2010) · Cell · doi:10.1016/j.cell.2010.02.026 · Cited by 1,211 · see citing works
Mechanisms of Muscle Wasting — The Role of the Ubiquitin–Proteasome Pathway
Mitch, W. E., & Goldberg, A. L. (1996) · New England Journal of Medicine · doi:10.1056/nejm199612193352507 · Cited by 1,163 · see citing works
The role of exercise and PGC1α in inflammation and chronic disease
Handschin, C., & Spiegelman, B. M. (2008) · Nature · doi:10.1038/nature07206 · Cited by 1,083 · see citing works
The Molecular Basis of Skeletal Muscle Atrophy
Jackman, R. W., & Kandarian, S. C. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00579.2003 · Cited by 1,008 · see citing works
Sandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z. P., Lecker, S. H., Goldberg, A. L., & Spiegelman, B. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607795103 · Cited by 974 · see citing works
Mitochondrial Fusion and Fission in Mammals
Chan, D. C. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104638 · Cited by 972 · see citing works
Du, J., Wang, X., Miereles, C., Bailey, J. L., Debigaré, R., Zheng, B., Price, S. R., & Mitch, W. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci18330 · Cited by 730 · see citing works
Overexpression of Atg5 in mice activates autophagy and extends lifespan
Pyo, J.-O., Yoo, S.-M., Ahn, H.-H., Nah, J., Hong, S.-H., Kam, T.-I., Jung, S., & Jung, Y.-K. (2013) · Nature Communications · doi:10.1038/ncomms3300 · Cited by 721 · see citing works
Mitochondrial fission and remodelling contributes to muscle atrophy
Romanello, V., Guadagnin, E., Gomes, L., Roder, I., Sandri, C., Petersen, Y., Milan, G., Masiero, E., Del Piccolo, P., Foretz, M., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.60 · Cited by 596 · see citing works
FoxO transcription factors: their roles in the maintenance of skeletal muscle homeostasis
Sanchez, A. M. J., Candau, R. B., & Bernardi, H. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1513-z · Cited by 335 · see citing works
Sanchez, A. M. J., Csibi, A., Raibon, A., Cornille, K., Gay, S., Bernardi, H., & Candau, R. B. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23399 · Cited by 329 · see citing works
Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy
Calvani, R., Joseph, A.-M., Adhihetty, P. J., Miccheli, A., Bossola, M., Leeuwenburgh, C., Bernabei, R., & Marzetti, E. (2013) · bchm · doi:10.1515/hsz-2012-0247 · Cited by 328 · see citing works
Yun, J., Puri, R., Yang, H. M., Lizzio, M. A., Wu, C., Sheng, Z., & Guo, M. (2014) · eLife · doi:10.7554/elife.01958 · Cited by 325 · see citing works
Cannavino, J., Brocca, L., Sandri, M., Bottinelli, R., & Pellegrino, M. A. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.275545 · Cited by 220 · see citing works
Cell death in denervated skeletal muscle is distinct from classical apoptosis
Borisov, A. B., & Carlson, B. M. (2000) · The Anatomical Record · doi:10.1002/(sici)1097-0185(20000301)258:3 · Cited by 173 · see citing works
PGC-1α buffers ROS-mediated removal of mitochondria during myogenesis
Baldelli, S., Aquilano, K., & Ciriolo, M. R. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.458 · Cited by 171 · see citing works
Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats
Siu, P. M., Pistilli, E. E., & Alway, S. E. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00198.2005 · Cited by 170 · see citing works
The role of PGC-1α on mitochondrial function and apoptotic susceptibility in muscle
Adhihetty, P. J., Uguccioni, G., Leick, L., Hidalgo, J., Pilegaard, H., & Hood, D. A. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00070.2009 · Cited by 168 · see citing works
Hickson-Bick, D. L. M., Jones, C. E., & Buja, L. M. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.10.013 · Cited by 133 · see citing works
Ros‐mediated activation of NF‐κB and Foxo during muscle disuse
Dodd, S. L., Gagnon, B. J., Senf, S. M., Hain, B. A., & Judge, A. R. (2010) · Muscle & Nerve · doi:10.1002/mus.21526 · Cited by 131 · see citing works
Cellular adaptations in soleus muscle during recovery after hindlimb unloading
Oishi, Y., Ogata, T., Yamamoto, K., Terada, M., Ohira, T., Ohira, Y., Taniguchi, K., & Roy, R. R. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01747.x · Cited by 93 · see citing works
Kang, C., Goodman, C. A., Hornberger, T. A., & Ji, L. L. (2015) · The FASEB Journal · doi:10.1096/fj.14-266619 · Cited by 92 · see citing works
Self-citationVazeille, E., Codran, A., Claustre, A., Avérous, J., Listrat, A., Béchet, D., Taillandier, D., Dardevet, D. P., Attaix, D., & Combaret, L. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90532.2008 · Cited by 81 · see citing works
Kang, C., & Ji, L. L. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01354.2012 · Cited by 71 · see citing works
Self-citationLiu, J., Peng, Y., Feng, Z., Shi, W., Qu, L., Li, Y., Liu, J., & Long, J. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.01.003 · Cited by 55 · see citing works
Wang, P., Li, C. G., Qi, Z., Cui, D., & Ding, S. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/536456 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Muscle metabolism and atrophy: let’s talk about sex
Rosa-Caldwell, M. E., & Greene, N. P. (2019) · Biology of Sex Differences · doi:10.1186/s13293-019-0257-3 · Cited by 202 · see citing works
Unravelling the mechanisms regulating muscle mitochondrial biogenesis
Hood, D. A., Tryon, L. D., Carter, H. N., Kim, Y., & Chen, C. C. W. (2016) · Biochemical Journal · doi:10.1042/bcj20160009 · Cited by 159 · see citing works
Mitochondria initiate and regulate sarcopenia
Alway, S. E., Mohamed, J. S., & Myers, M. J. (2017) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000101 · Cited by 153 · see citing works
“However, overexpression of PGC-1α was reported to attenuate Pink1 levels in response to remobilization of muscle (67).”
BackgroundYeo, D., Kang, C., Gomez-Cabrera, M. C., Vina, J., & Ji, L. L. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.456 · Cited by 137 · see citing works
Self-citationFrom mitochondria to sarcopenia: role of 17β-estradiol and testosterone
Tian, X., Lou, S., & Shi, R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1156583 · Cited by 54 · see citing works
Long-Term PGC1β Overexpression Leads to Apoptosis, Autophagy and Muscle Wasting
Sopariwala, D. H., Yadav, V., Badin, P.-M., Likhite, N., Sheth, M., Lorca, S., Vila, I. K., Kim, E. R., Tong, Q., Song, M. S., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10238-9 · Cited by 14 · see citing works
- Authors
- Kang, C., & Ji, L. L.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Ji, Li Li
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 93
- Pages
- 32-40
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2212789884
- Cited by
- 83
- References
- 37
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 13 · 2019: 11 · 2018: 12 · 2017: 4 · 2016: 9
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- PGC-1α, mitophagy, disuse atrophy, immobilization, remobilization, tibialis anterior, mitochondrial biogenesis, PINK1, Parkin, mitofusin 2, FOXO, autophagy-lysosome pathway, oxidative stress, mitochondrial ubiquitination, apoptosis, in vivo transfection
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, DNA, Mitochondrial, Gene Expression Regulation, Humans, Mitochondria, Muscular Diseases, Oxidation-Reduction, Transfection, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Muscular Disorders, Atrophic, Mice, Mitophagy
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
