High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagy
Open accessAbstract
An increasing body of evidence points to mitochondrial dysfunction as a contributor to the molecular pathogenesis of neurodegenerative diseases such as Parkinson's disease. Recent studies of the Parkinson's disease associated genes PINK1 (ref. 2) and parkin (PARK2, ref. 3) indicate that they may act in a quality control pathway preventing the accumulation of dysfunctional mitochondria. Here we elucidate regulators that have an impact on parkin translocation to damaged mitochondria with genome-wide small interfering RNA (siRNA) screens coupled to high-content microscopy. Screening yielded gene candidates involved in diverse cellular processes that were subsequently validated in low-throughput assays. This led to characterization of TOMM7 as essential for stabilizing PINK1 on the outer mitochondrial membrane following mitochondrial damage. We also discovered that HSPA1L (HSP70 family member) and BAG4 have mutually opposing roles in the regulation of parkin translocation. The screens revealed that SIAH3, found to localize to mitochondria, inhibits PINK1 accumulation after mitochondrial insult, reducing parkin translocation. Overall, our screens provide a rich resource to understand mitochondrial quality control.
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?
Multiple genome-wide siRNA/CRISPR-Cas9 screens have identified mitophagy genes with little overlap between studies.
“Multiple genome-wide siRNA/CRISPR-Cas9 screens have already identified mitophagy genes although with little overlap between studies [15–18].”
From miRNA family miR-29 inhibits PINK1-PRKN signaling via ATG9A (2026) · cites this paper as [16]
The paper reports genome-wide siRNA screens that identified regulators of parkin upstream of mitophagy (conclusion, page unavailable). Its candidate-selection passage says 24 candidates overlapped between its own pooled and non-pooled screens, but it does not establish little overlap between different studies; it also does not report a CRISPR-Cas9 screen. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227 · see citing works
Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
Narendra, D., Tanaka, A., Suen, D.-F., & Youle, R. J. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200809125 · Cited by 4,026 · see citing works
Self-citationHereditary 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
PINK1 Is Selectively Stabilized on Impaired Mitochondria to Activate Parkin
Narendra, D. P., Jin, S. M., Tanaka, A., Suen, D.-F., Gautier, C. A., Shen, J., Cookson, M. R., & Youle, R. J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000298 · Cited by 2,944 · see citing works
Self-citationPINK1/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
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
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
Self-citationLandscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
Sarraf, S. A., Raman, M., Guarani, V., Sowa, M. E., Huttlin, E. L., Gygi, S. P., & Harper, J. W. (2013) · Nature · doi:10.1038/nature12043 · Cited by 1,020 · see citing works
Broad activation of the ubiquitin–proteasome system by Parkin is critical for mitophagy
Chan, N. C., Salazar, A. M., Pham, A. H., Sweredoski, M. J., Kolawa, N. J., Graham, R. L. J., Hess, S., & Chan, D. C. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr048 · Cited by 993 · see citing works
Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarity
Jackson, A. L., Burchard, J., Schelter, J. M., Chau, B. N., Cleary, M. A., Lim, L. P., & Linsley, P. S. (2006) · RNA · doi:10.1261/rna.25706 · Cited by 953 · see citing works
3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets
Birmingham, A., Anderson, E. M., Reynolds, A., Ilsley-Tyree, D., Leake, D., Fedorov, Y., Baskerville, S., Maksimova, E., Robinson, K., Karpilow, J., et al. (2006) · Nature Methods · doi:10.1038/nmeth854 · Cited by 920 · see citing works
Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress
Gautier, C. A., Kitada, T., & Shen, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802076105 · Cited by 698 · see citing works
Lazarou, M., Jin, S. M., Kane, L. A., & Youle, R. J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2011.12.014 · Cited by 670 · see citing works
Self-citationThe PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo
Vincow, E. S., Merrihew, G., Thomas, R. E., Shulman, N. J., Beyer, R. P., MacCoss, M. J., & Pallanck, L. J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1221132110 · Cited by 478 · see citing works
Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies
Bushman, F. D., Malani, N., Fernandes, J. D., D’Orso, I., Cagney, G., Diamond, T. L., Zhou, H., Hazuda, D. J., Espeseth, A. S., König, R., et al. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000437 · Cited by 452 · see citing works
Parkin overexpression selects against a deleterious mtDNA mutation in heteroplasmic cybrid cells
Suen, D., Narendra, D. P., Tanaka, A., Manfredi, G., & Youle, R. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914569107 · Cited by 335 · see citing works
Self-citationHageman, J., & Kampinga, H. (2008) · Cell stress & chaperones (Print) · doi:10.1007/s12192-008-0060-2 · Cited by 203 · see citing works
BAG5 Inhibits Parkin and Enhances Dopaminergic Neuron Degeneration
Kalia, S. K., Lee, S., Smith, P. D., Liu, L., Crocker, S. J., Thorarinsdottir, T., Glover, J. R., Fon, E. A., Park, D. S., & Lozano, A. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.11.026 · Cited by 201 · see citing works
Molecular and clinical prodrome of Parkinson disease: implications for treatment
Schapira, A. H. V., & TOLOSA, E. S. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.52 · Cited by 199 · see citing works
Simpson, J. C., Joggerst, B., Laketa, V., Verissimo, F., Cetin, C., Erfle, H., Bexiga, M. G., Singan, V. R., Hériché, J.-K., Neumann, B., et al. (2012) · Nature Cell Biology · doi:10.1038/ncb2510 · Cited by 186 · see citing works
Vigilance and Validation: Keys to Success in RNAi Screening
Sigoillot, F. D., & King, R. W. (2010) · ACS Chemical Biology · doi:10.1021/cb100358f · Cited by 128 · see citing works
Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster
Pimenta de Castro, I., Costa, A. C., Lam, D., Tufi, R., Fedele, V, Moisoi, N., Dinsdale, D., Deas, E., Loh, S. H. Y., & Martins, L. M. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2012.5 · Cited by 128 · see citing works
C911: A Bench-Level Control for Sequence Specific siRNA Off-Target Effects
Buehler, E., Chen, Y.-C., & Martin, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051942 · Cited by 116 · see citing works
Self-citationParkin mediates the degradation‐independent ubiquitination of Hsp70
Moore, D. J., West, A. B., Dikeman, D. A., Dawson, V. L., & Dawson, T. M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05261.x · Cited by 101 · see citing works
Schultz, N., Marenstein, D. R., de Angelis, D. D., Wang, W.-Q., Nelander, S., Jacobsen, A., Marks, D., Massagué, J., & Sander, C. (2011) · Silence · doi:10.1186/1758-907x-2-3 · Cited by 93 · see citing works
Burman, J. L., Yu, S., Poole, A. C., Decal, R. B., & Pallanck, L. J. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120688109 · Cited by 72 · see citing works
siRNA off-target effects in genome-wide screens identify signaling pathway members
Buehler, E., Khan, A. A., Marine, S. D., Rajaram, M., Bahl, A., Burchard, J., & Ferrer, M. (2012) · Scientific Reports · doi:10.1038/srep00428 · Cited by 69 · see citing works
Self-citationCommon Seed Analysis to Identify Off-Target Effects in siRNA Screens
Marine, S., Bahl, A., Ferrer, M., & Buehler, E. C. (2011) · SLAS DISCOVERY · doi:10.1177/1087057111427348 · Cited by 66 · see citing works
Self-citationKato, H., & Mihara, K. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.02.150 · Cited by 55 · see citing works
Sudbery, I. M., Enright, A. J., Fraser, A. G., & Dunham, I. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-175 · Cited by 46 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
Lazarou, M., Sliter, D. A., Kane, L. A., Sarraf, S. A., Wang, C., Burman, J. L., Sideris, D. P., Fogel, A. I., & Youle, R. J. (2015) · Nature · doi:10.1038/nature14893 · Cited by 2,774 · see citing works
Self-citationThe Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310 · see citing works
Self-citationMitophagy and Quality Control Mechanisms in Mitochondrial Maintenance
Pickles, S., Vigié, P., & Youle, R. J. (2018) · Current Biology · doi:10.1016/j.cub.2018.01.004 · Cited by 2,081 · see citing works
Self-citationMechanisms of mitophagy in cellular homeostasis, physiology and pathology
Palikaras, K., Lionaki, E., & Tavernarakis, N. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0176-2 · Cited by 1,505 · see citing works
PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity
Kane, L. A., Lazarou, M., Fogel, A. I., Li, Y., Yamano, K., Sarraf, S. A., Banerjee, S., & Youle, R. J. (2014) · Journal of Cell Biology · doi:10.1083/jcb.201402104 · Cited by 1,298 · see citing works
Self-citationGenome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening
Joung, J., Konermann, S., Gootenberg, J. S., Abudayyeh, O. O., Platt, R. J., Brigham, M. D., Sanjana, N. E., & Zhang, F. (2017) · Nature Protocols · doi:10.1038/nprot.2017.016 · Cited by 1,243 · see citing works
High-throughput functional genomics using CRISPR-Cas9
Shalem, O., Sanjana, N. E., & Zhang, F. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3899 · Cited by 1,233 · see citing works
Mitochondrial dynamics and mitochondrial quality control
Ni, H.-M., Williams, J. A., & Ding, W.-X. (2015) · Redox Biology · doi:10.1016/j.redox.2014.11.006 · Cited by 931 · see citing works
Deciphering the Molecular Signals of PINK1/Parkin Mitophagy
Nguyen, T. N., Padman, B. S., & Lazarou, M. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.05.008 · Cited by 732 · see citing works
Ordureau, A., Sarraf, S. A., Duda, D. M., Heo, J., Jedrychowski, M. P., Sviderskiy, V. O., Olszewski, J. L., Koerber, J. T., Xie, T., Beausoleil, S. A., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.09.007 · Cited by 693 · see citing works
Wang, Y., Bryant, S. H., Cheng, T., Wang, J., Gindulytė, A., Shoemaker, B. A., Thiessen, P. A., He, S., & Zhang, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1118 · Cited by 675 · see citing works
PINK1/Parkin-mediated mitophagy in mammalian cells
Eiyama, A., & Okamoto, K. (2015) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2015.01.002 · Cited by 603 · see citing works
MitoFates: Improved Prediction of Mitochondrial Targeting Sequences and Their Cleavage Sites*
Fukasawa, Y., Tsuji, J., Fu, S.-C., Tomii, K., Horton, P., & Imai, K. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.043083 · Cited by 555 · see citing works
The Role of Autophagy in the Heart
Sciarretta, S., Maejima, Y., Zablocki, D., & Sadoshima, J. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121427 · Cited by 547 · see citing works
Crosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System
Kocatürk, N. M., & Gözüaçık, D. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00128 · Cited by 415 · see citing works
PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis
Yan, C., Gong, L., Chen, L., Xu, M., Abou‐Hamdan, H., Tang, M., Désaubry, L., & Song, Z. (2019) · Autophagy · doi:10.1080/15548627.2019.1628520 · Cited by 416 · see citing works
The three ‘P’s of mitophagy: PARKIN.; PINK1.; and post-translational modifications
Durcan, T. M., & Fon, E. A. (2015) · Genes & Development · doi:10.1101/gad.262758.115 · Cited by 400 · see citing works
AMBRA1 is able to induce mitophagy via LC3 binding, regardless of PARKIN and p62/SQSTM1
Strappazzon, F., Nazio, F., Corrado, M., Cianfanelli, V, Romagnoli, A., Fimia, G. M., Campello, S., Nardacci, R., Piacentini, M., Campanella, M., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.139 · Cited by 399 · see citing works
Parkin and PINK1: much more than mitophagy
Scarffe, L. A., Stevens, D. A., Dawson, V. L., & Dawson, T. M. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.03.004 · Cited by 392 · see citing works
PINK1/Parkin-mediated mitophagy in neurodegenerative diseases
Li, J., Yang, D., Li, Z., Zhao, M., Wang, D., Sun, Z., Wen, P., Dai, Y., Gou, F., Ji, Y., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101817 · Cited by 388 · see citing works
Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond
Bingol, B., & Sheng, M. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.015 · Cited by 333 · see citing works
USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria
Cunningham, C. N., Baughman, J. M., Phu, L., Tea, J. S., Yu, C., Coons, M. M., Kirkpatrick, D. S., Bingol, B., & Corn, J. E. (2015) · Nature Cell Biology · doi:10.1038/ncb3097 · Cited by 329 · see citing works
PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol
Sekine, S., & Youle, R. J. (2018) · BMC Biology · doi:10.1186/s12915-017-0470-7 · Cited by 308 · see citing works
Self-citationRegulation of Mitochondrial ATP Production: Ca2+ Signaling and Quality Control
Boyman, L., Karbowski, M., & Lederer, W. J. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.10.007 · Cited by 309 · see citing works
Mitochondrial quality control in health and in Parkinson’s disease
Eldeeb, M. A., Thomas, R. A., Ragheb, M. A., Fallahi, A., & Fon, E. A. (2022) · Physiological Reviews · doi:10.1152/physrev.00041.2021 · Cited by 276 · see citing works
Phosphorylated ubiquitin chain is the genuine Parkin receptor
Okatsu, K., Koyano, F., Kimura, M., Kosako, H., Saeki, Y., Tanaka, K., & Matsuda, N. (2015) · The Journal of Cell Biology · doi:10.1083/jcb.201410050 · Cited by 261 · see citing works
The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation
Yamano, K., Matsuda, N., & Tanaka, K. (2016) · EMBO Reports · doi:10.15252/embr.201541486 · Cited by 239 · see citing works
Self-citationThe ADP/ATP translocase drives mitophagy independent of nucleotide exchange
Hoshino, A., Wang, W.-J., Wada, S., McDermott-Roe, C., Evans, C. S., Gosis, B., Morley, M. P., Rathi, K. S., Li, J., Li, K., et al. (2019) · Nature · doi:10.1038/s41586-019-1667-4 · Cited by 228 · see citing works
Organellophagy: Eliminating cellular building blocks via selective autophagy
Okamoto, K. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201402054 · Cited by 218 · see citing works
Macdonald, R., Barnes, K., Hastings, C., & Mortiboys, H. (2018) · Biochemical Society Transactions · doi:10.1042/bst20170501 · Cited by 216 · see citing works
Mechanisms and roles of mitophagy in neurodegenerative diseases
Wang, Y., Liu, N., & Lu, B. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13140 · Cited by 214 · see citing works
Gan, Z. Y., Callegari, S., Cobbold, S. A., Cotton, T. R., Mlodzianoski, M. J., Schubert, A. F., Geoghegan, N. D., Rogers, K. L., Leis, A. P., Dewson, G., et al. (2021) · Nature · doi:10.1038/s41586-021-04340-2 · Cited by 209 · see citing works
Critical role of mitochondrial ubiquitination and the OPTN–ATG9A axis in mitophagy
Yamano, K., Kikuchi, R., Kojima, W., Hayashida, R., Koyano, F., Kawawaki, J., Shoda, T., Demizu, Y., Naito, M., Tanaka, K., et al. (2020) · Journal of Cell Biology · doi:10.1083/jcb.201912144 · Cited by 205 · see citing works
Self-citationThe multifaceted regulation of mitophagy by endogenous metabolites
Zhang, T., Liu, Q., Gao, W., Sehgal, S. A., & Wu, H. (2021) · Autophagy · doi:10.1080/15548627.2021.1975914 · Cited by 207 · see citing works
Truban, D., Hou, X., Caulfield, T. R., Fiesel, F. C., & Springer, W. (2016) · Journal of Parkinson’s Disease · doi:10.3233/jpd-160989 · Cited by 237 · see citing works
Mitochondrial proteostasis in the context of cellular and organismal health and aging
Moehle, E. A., Shen, K., & Dillin, A. G. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.tm117.000893 · Cited by 193 · see citing works
Autophagy Assays for Biological Discovery and Therapeutic Development
Mizushima, N., & Murphy, L. O. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.07.006 · Cited by 192 · see citing works
The Mitochondrial Dynamism-Mitophagy-Cell Death Interactome
Dorn, G. W., & Kitsis, R. N. (2014) · Circulation Research · doi:10.1161/circresaha.116.303554 · Cited by 185 · see citing works
Pink1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy
Pryde, K. R., Smith, H. L., Chau, K.-Y., & Schapira, A. H. V. (2016) · Journal of Cell Biology · doi:10.1083/jcb.201509003 · Cited by 185 · see citing works
Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration
Katayama, H., Hama, H., Nagasawa, K., Kurokawa, H., Sugiyama, M., Ando, R., Funata, M., Yoshida, N., Homma, M., Nishimura, T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.025 · Cited by 180 · see citing works
Genetics and genomics of Parkinson’s disease
Lin, M. K., & Farrer, M. J. (2014) · Genome Medicine · doi:10.1186/gm566 · Cited by 179 · see citing works
Reciprocal Roles of Tom7 and OMA1 during Mitochondrial Import and Activation of PINK1
Sekine, S., Wang, C., Sideris, D. P., Bunker, E. N., Zhang, Z., & Youle, R. J. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.01.002 · Cited by 160 · see citing works
Self-citationMitochondrial pathology: stress signals from the energy factory
Raimundo, N. (2014) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.01.005 · Cited by 164 · see citing works
Guo, S., Liang, Y., Murphy, S. F., Huang, A., Shen, H., Kelly, D. F., Sobrado, P., & Sheng, Z. (2015) · Autophagy · doi:10.1080/15548627.2015.1017181 · Cited by 157 · see citing works
Mohanty, A., Tiwari-Pandey, R., & Pandey, N. R. (2019) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-019-00507-9 · Cited by 157 · see citing works
Leonard, A. P., Cameron, R. B., Speiser, J. L., Wolf, B. J., Peterson, Y. K., Schnellmann, R. G., Beeson, C. C., & Rohrer, B. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.11.002 · Cited by 150 · see citing works
Parkin and mitochondrial quality control: toward assembling the puzzle
Winklhofer, K. F. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.01.001 · Cited by 149 · see citing works
Wilson, E. L., & Metzakopian, E. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00705-8 · Cited by 147 · see citing works
Li, J., Zhu, S., Kozono, D., Ng, K., Futalan, D., Shen, Y. H., Akers, J. C., Steed, T., Kushwaha, D. S., Schlabach, M. R., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1801 · Cited by 145 · see citing works
AMPK protects against alcohol-induced liver injury through UQCRC2 to up-regulate mitophagy
Lü, X., Xuan, W., Li, J., Yao, H., Huang, C., & Li, J. (2021) · Autophagy · doi:10.1080/15548627.2021.1886829 · Cited by 145 · see citing works
Self-citationROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway
Moskal, N., Riccio, V., Bashkurov, M., Taddese, R., Datti, A., Lewis, P. N., & Angus McQuibban, G. (2020) · Nature Communications · doi:10.1038/s41467-019-13781-3 · Cited by 142 · see citing works
Feng, S., Wang, Z., Yuan, Y., Wang, X., Sun, H., Chen, N., & Zhang, Y. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104553 · Cited by 140 · see citing works
Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases
Corti, O., Blomgren, K., Poletti, A., & Beart, P. M. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15002 · Cited by 141 · see citing works
PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma
Agnihotri, S., Golbourn, B. J., Huang, X., Remke, M., Younger, S. H., Cairns, R. A., Chalil, A., Smith, C. A., Krumholtz, S.-L., Mackenzie, D., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3079 · Cited by 139 · see citing works
Madhu, V., Boneski, P. K., Silagi, E. S., Qiu, Y., Kurland, I. J., Guntur, A. R., Shapiro, I. M., & Risbud, M. V. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.4019 · Cited by 134 · see citing works
Mitochondrial genome maintenance in health and disease
Copeland, W. C., & Longley, M. J. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.03.010 · Cited by 137 · see citing works
Mitophagy mechanisms and role in human diseases
Redmann, M., Dodson, M. B., Boyer‐Guittaut, M., Darley-Usmar, V. M., & Zhang, J. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.05.010 · Cited by 136 · see citing works
Zhang, J. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.003 · Cited by 134 · see citing works
Okatsu, K., Kimura, M., Oka, T., Tanaka, K., & Matsuda, N. (2015) · Journal of Cell Science · doi:10.1242/jcs.161000 · Cited by 127 · see citing works
Miller, S., & Muqit, M. M. K. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.04.029 · Cited by 129 · see citing works
Xie, X., Yang, Y., Wang, Q., Liu, H.-F., Fang, X., Li, C., Jiang, Y., Wang, S., Zhao, H., Miao, J., et al. (2023) · Cell Research · doi:10.1038/s41422-022-00766-z · Cited by 127 · see citing works
Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease
Lim, J., Li, L., Kakhlon, O., Myerowitz, R., & Raben, N. (2015) · Autophagy · doi:10.1080/15548627.2015.1009779 · Cited by 125 · see citing works
Khurana, V., Peng, J., Chung, C. Y., Auluck, P. K., Fanning, S., Tardiff, D. F., Bartels, T., Koeva, M., Eichhorn, S. W., Benyamini, H., et al. (2017) · Cell Systems · doi:10.1016/j.cels.2016.12.011 · Cited by 121 · see citing works
Hypoxia Activation of Mitophagy and Its Role in Disease Pathogenesis
Wu, H., & Chen, Q. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6204 · Cited by 118 · see citing works
Mitophagy for cardioprotection
Titus, A. S., Sung, E., Zablocki, D., & Sadoshima, J. (2023) · Basic Research in Cardiology · doi:10.1007/s00395-023-01009-x · Cited by 121 · see citing works
Palmer, C. S., Anderson, A. J., & Stojanovski, D. (2020) · FEBS Letters · doi:10.1002/1873-3468.14022 · Cited by 120 · see citing works
Iron loss triggers mitophagy through induction of mitochondrial ferritin
Hara, Y., Yanatori, I., Tanaka, A., Kishi, F., Lemasters, J. J., Nishina, S., Sasaki, K., & Hino, K. (2020) · EMBO Reports · doi:10.15252/embr.202050202 · Cited by 114 · see citing works
BRCA1 and S phase DNA repair pathways restrict LINE-1 retrotransposition in human cells
Mita, P., Sun, X., Fenyö, D., Kahler, D. J., Li, D., Agmon, N., Wudzinska, A., Keegan, S., Bader, J. S., Yun, C., et al. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0374-z · Cited by 113 · see citing works
Mechanism of PINK1 activation by autophosphorylation and insights into assembly on the TOM complex
Rasool, S., Veyron, S., Soya, N., Eldeeb, M. A., Lukács, G. L., Fon, E. A., & Trempe, J. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.11.012 · Cited by 110 · see citing works
Meißner, C., Lorenz, H., Hehn, B., & Lemberg, M. K. (2015) · Autophagy · doi:10.1080/15548627.2015.1063763 · Cited by 111 · see citing works
PINK1 deficiency sustains cell proliferation by reprogramming glucose metabolism through HIF1
Requejo-Aguilar, R., López-Fabuel, I., Fernández, E., Martins, L. M., Almeida, Á., & Bolaños, J. P. (2014) · Nature Communications · doi:10.1038/ncomms5514 · Cited by 112 · see citing works
Mechanisms of PINK1, ubiquitin and Parkin interactions in mitochondrial quality control and beyond
Bayne, A. N., & Trempe, J. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03203-4 · Cited by 113 · see citing works
Henstridge, D. C., Whitham, M., & Febbraio, M. A. (2014) · Molecular Metabolism · doi:10.1016/j.molmet.2014.08.003 · Cited by 110 · see citing works
Caulfield, T. R., Fiesel, F. C., Moussaud-Lamodière, E. L., Dourado, D. F. A. R., Flores, S. C., & Springer, W. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003935 · Cited by 108 · see citing works
High-Throughput Imaging for the Discovery of Cellular Mechanisms of Disease
Pegoraro, G., & Misteli, T. (2017) · Trends in Genetics · doi:10.1016/j.tig.2017.06.005 · Cited by 103 · see citing works
Ubiquitin and Receptor-Dependent Mitophagy Pathways and Their Implication in Neurodegeneration
Fritsch, L. E., Moore, M. E., Sarraf, S. A., & Pickrell, A. M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.10.015 · Cited by 104 · see citing works
Mitophagy in Cardiovascular Diseases
Morciano, G., Patergnani, S., Bonora, M., Pedriali, G., Tarocco, A., Bouhamida, E., Marchi, S., Ancora, G., Anania, G., Wieckowski, M. R., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9030892 · Cited by 106 · see citing works
The role of mitochondrial dynamics in oocyte and early embryo development
Yildirim, R. M., & Seli, E. U. (2024) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2024.01.007 · Cited by 106 · see citing works
Mitochondrial protein translocases for survival and wellbeing
Sokòl, A. M., Sztolsztener, M. E., Wasilewski, M., Heinz, E., & Chacińska, A. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.05.028 · Cited by 102 · see citing works
Potting, C., Crochemore, C., Moretti, F., Nigsch, F., Schmidt, I., Manneville, C., Carbone, W., Knehr, J., DeJesus, R., Lindeman, A., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711023115 · Cited by 93 · see citing works
Madhu, V., Hernandez-Meadows, M., Boneski, P. K., Qiu, Y., Guntur, A. R., Kurland, I. J., Barve, R. A., & Risbud, M. V. (2023) · Autophagy · doi:10.1080/15548627.2022.2162245 · Cited by 96 · see citing works
The mitochondrial kinase PINK 1: functions beyond mitophagy
Voigt, A., Berlemann, L. A., & Winklhofer, K. F. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13655 · Cited by 98 · see citing works
Lee, J. H., Yoon, Y. M., Song, K., Noh, H., & Lee, S. H. (2020) · Aging Cell · doi:10.1111/acel.13111 · Cited by 97 · see citing works
Cherok, E., Xu, S., Li, S., Das, S., Meltzer, W. A., Zalzman, M., Wang, C., & Karbowski, M. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-04-0208 · Cited by 94 · see citing works
Self-citationPellegrino, M. W., & Haynes, C. M. (2015) · BMC Biology · doi:10.1186/s12915-015-0129-1 · Cited by 91 · see citing works
A novel role of KEAP1/PGAM5 complex: ROS sensor for inducing mitophagy
Zeb, A., Choubey, V., Gupta, R., Kuum, M., Safiulina, D., Vaarmann, A., Gogichaishvili, N., Liiv, M., Ilves, I., Tämm, K., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102186 · Cited by 92 · see citing works
Keeping the immune system in check: a role for mitophagy
Lazarou, M. (2014) · Immunology and Cell Biology · doi:10.1038/icb.2014.75 · Cited by 92 · see citing works
Protein trafficking at the crossroads to mitochondria
Wasilewski, M., Chojnacka, K., & Chacińska, A. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.10.019 · Cited by 89 · see citing works
Ito, H., Tanaka, S., Akiyama, Y., Shimada, S., Adikrisna, R., Matsumura, S., Aihara, A., Mitsunori, Y., Ban, D., Ochiai, T., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146564 · Cited by 81 · see citing works
Dynamic changes of muscle insulin sensitivity after metabolic surgery
Gancheva, S., Ouni, M., Jeleník, T., Koliaki, C. C., Szendroedi, J., Toledo, F. G. S., Markgraf, D. F., Pesta, D. H., Mastrototaro, L., Filippo, E. D., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12081-0 · Cited by 78 · see citing works
Selective autophagy as a therapeutic target for neurological diseases
Xu, W., Ocak, U., Gao, L., Tu, S., Lenahan, C., Zhang, J., & Shao, A. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03667-9 · Cited by 82 · see citing works
Heman-Ackah, S. M., Bassett, A. R., & Wood, M. J. A. (2016) · Scientific Reports · doi:10.1038/srep28420 · Cited by 77 · see citing works
Self-citationEldeeb, M. A., Bayne, A. N., Fallahi, A., Goiran, T., MacDougall, E. J., Soumbasis, A., Zorca, C. E., Jones-Tabah, J., Thomas, R. A., Karpilovsky, N. C., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2313540121 · Cited by 80 · see citing works
Application guide for omics approaches to cell signaling
Yao, Z., Petschnigg, J., Ketteler, R., & Štagljar, I. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1809 · Cited by 76 · see citing works
Kravic, B., Harbauer, A. B., Romanello, V., Simeone, L., Vögtle, F.-N., Kaiser, T., Straubinger, M., Huraskin, D., Böttcher, M., Cerqua, C., et al. (2018) · Autophagy · doi:10.1080/15548627.2017.1403716 · Cited by 75 · see citing works
PubChem applications in drug discovery: a bibliometric analysis
Cheng, T., Pan, Y., Hao, M., Wang, Y., & Bryant, S. H. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.08.008 · Cited by 74 · see citing works
PTENα regulates mitophagy and maintains mitochondrial quality control
Li, G., Yang, J., Yang, C., Zhu, M., Jin, Y., McNutt, M. A., & Yin, Y. (2018) · Autophagy · doi:10.1080/15548627.2018.1489477 · Cited by 75 · see citing works
Heo, J., Harper, N. J., Paulo, J. A., Li, M. Z., Xu, Q., Coughlin, M. L., Elledge, S. J., & Harper, J. W. (2019) · Science Advances · doi:10.1126/sciadv.aay4624 · Cited by 73 · see citing works
Toward stem cell-based phenotypic screens for neurodegenerative diseases
Khurana, V., Tardiff, D. F., Chung, C. Y., & Lindquist, S. L. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.79 · Cited by 70 · see citing works
Select E2 enzymes differentially regulate parkin activation and mitophagy
Fiesel, F. C., Moussaud-Lamodière, E. L., Ando, M., & Springer, W. (2014) · Journal of Cell Science · doi:10.1242/jcs.147520 · Cited by 72 · see citing works
- Authors
- Hasson, S. A., Kane, L. A., Yamano, K., Huang, C.-H., Sliter, D. A., Buehler, E., Wang, C., Heman-Ackah, S. M., Hessa, T., Guha, R., Martin, S. E., & Youle, R. J.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Youle, Richard J.
- ORCID
- Venue
- Nature
- Published
- 2013-11-24
- Volume
- 504
- Issue
- 7479
- Pages
- 291-295
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5841086
- OpenAlex
- W2091264505
- Cited by
- 365
- References
- 30
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 25 · 2023: 16 · 2022: 27 · 2021: 36 · 2020: 32 · 2019: 38 · 2018: 27 · 2017: 27 · 2016: 31 · 2015: 36 · 2014: 36
- FWCI
- 21.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- Funders
- National Institutes of Health (Z99 NS999999)
- National Institute of General Medical Sciences
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitophagy, Parkin, PINK1, mitochondrial quality control, HSPA1L, mitochondrial outer membrane, Parkinson's disease, mitochondrial dysfunction, autophagy, ubiquitin ligase
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, PTEN-Induced Putative Kinase, Multigene Family, HeLa Cells, Humans, Membrane Proteins, Mitochondria, Parkinson Disease, Protein Kinases, Reproducibility of Results, Genome, Human, HSP70 Heat-Shock Proteins, Protein Transport, Mitochondrial Proteins, RNA Interference, RNA, Small Interfering, Ubiquitin-Protein Ligases, HCT116 Cells, Adaptor Proteins, Signal Transducing, Mitochondrial Membranes, HEK293 Cells, 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
