Overexpression of pink1 or parkin in indirect flight muscles promotes mitochondrial proteostasis and extends lifespan in Drosophila melanogaster
Open accessAbstract
Dysfunctional mitochondria have been implicated in aging and age-related disorders such as Parkinson's diseases (PD). We previously showed that pink1 and parkin, two familial PD genes, function in a linear pathway to maintain mitochondrial integrity and function. Studies of mammalian cell lines also suggest that these genes regulate mitochondrial autophagy(mitophagy). Overexpressing Parkin promotes proteostasis and function of aged muscles both in fruit flies and mice, and recent studies also indicated that mitochondrial ubiquitination are accumulated in aged muscles. However, the underlying mechanisms for pink1 and parkin mediated mitophagy on longevity is not fully understood. Here, we found that mitochondrial ubiquitination increased in indirect flight muscles (IFMs) in an age-dependent manner. Overexpression of pink1 or parkin in IFMs can abolish mitochondrial ubiquitination, restore ATP level and extend lifespan, while blocking autophagy via ATG1 knock-down suppress these effects in aged IFMs. Taken together, these results show that pink1/parkin promotes mitophagy of mitochondrial ubiquitination in aged muscles and extend lifespan in an Atg1-dependent manner. Our study provides physiological evidence that mitophagy of mitochondrial ubiquitination mediated by PINK1/ Parkin is crucial for muscle function and highlights the role of mitophagy in the pathogenesis of chronic diseases like PD.
AI snapshot
Written from the paper’s full text.
TL;DR
Overexpression of pink1 or parkin in Drosophila indirect flight muscles reduces age-dependent mitochondrial ubiquitination, restores ATP and climbing ability, and extends lifespan. These benefits require Atg1/autophagy, linking PINK1/Parkin-mediated mitophagy to muscle proteostasis and longevity.
Key findings
- Mitochondrial ubiquitination (FK2-positive puncta) increased with age in indirect flight muscles: few in 3–4-day-old flies, more at 14 days, and 2–5 μm puncta at 35 days; isolated mitochondria from 50-day-old flies had more FK2 signal than those from 5-day-old flies.
- Overexpressing pink1 or parkin in IFMs significantly reduced FK2-positive puncta at 35 days, restored muscle ATP levels, and improved climbing ability in aged flies.
- Lifespan was extended in IFMGal4;UAS-Pink1 flies (median 70.8 days, ~7.5% increase) and IFMGal4;UAS-ParkinC2 flies (median 73.5 days, ~11% increase) compared with controls (median 65.1 days).
- Atg1 knockdown substantially blocked Parkin’s rescue of mitochondrial ubiquitination, ATP level, climbing ability, and lifespan, indicating the effects are autophagy/Atg1-dependent.
Methods
- Drosophila genetics: IFMGal4-driven overexpression of pink1 or parkinC2, Atg1RNAi, Atg16A, and Ref(2)PGFP; lifespan assays housed 30 male or female flies per vial at 25°C, with ~100–120 flies per genotype scored.
- Imaging and biochemistry: FK2, ATP synthase, Tom20, mitoGFP, Ref(2)PGFP, Lysotracker, and Toluidine blue staining; ATP measured by luciferase bioluminescence and normalized to protein; climbing assay scored flies above 5 cm in 10 seconds.
- Statistics: one-way ANOVA or t-tests for most comparisons; log-rank (Mantel-Cox) test for survival.
Limitations
- The paper does not state a dedicated limitations section.
- Evident from the text: mitophagy is inferred from colocalization (Ref(2)P, Lysotracker) and Atg1 dependence rather than direct measurement of mitophagic flux.
- Evident from the text: findings are limited to Drosophila indirect flight muscles; no mammalian or other tissue validation is reported.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 16 cited sources checked · 0 supported · 0 flagged
- Findingown data
Mitochondrial ubiquitination increases in Drosophila indirect flight muscles with age.
“Here, we found that mitochondrial ubiquitination increased in indirect flight muscles (IFMs) in an age-dependent manner.”
- Also stated in: § Age-dependent increase of mitochondria ubiquitylation in Drosophila IFMs · plain
“As shown in Fig 1A, few FK2 positive foci were present in the muscles of young flies (3–4 days old), while size and number were significantly higher in the muscles of 14-day old flies and reached 2–5 μm in muscles of 35-day-old flies”
- Also stated in: § Age-dependent increase of mitochondria ubiquitylation in Drosophila IFMs · plain
“isolated mitochondria of throaces from aged flies (50 days old) have significant more FK2 signals compared with those in young flies (5 days old)”
Quote in the paperSubstantial claim- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
- Also stated in: § Age-dependent increase of mitochondria ubiquitylation in Drosophila IFMs · plain
- Findingown data
Overexpression of pink1 or parkin in indirect flight muscles restores climbing ability in aging animals.
“climbing ability reduced in aging animals was significantly restored by overexpressing Pink1 or Parkin in muscles”
Quote in the paperSubstantial claim - Findingown data
Overexpression of pink1 or parkin in indirect flight muscles restores ATP level in muscle fibers.
“the ATP level in muscle fiber was also significantly restored in Pink1 OE or ParkinC2 flies.”
Quote in the paperSubstantial claim- Rests on an assumption: Cellular ATP is mainly produced in mitochondria by oxidative phosphorylation.
- Findingown data
A subset of mitochondria in aged Drosophila indirect flight muscles are ubiquitylated.
“FK2 positive puncta are colocalized or intercalated with mitoGFP, suggesting a subset of mitochondria were ubiquitylated in muscles.”
- Also stated in: § Discussion · plain
“Rana et al. (2017) have shown that a subset of mitochondria are ubiquitinated in aged muscles [15]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] A Rana, 2017, Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster, Nat Commun source
Not checked in the free run.
- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
- Also stated in: § Discussion · plain
- Findingown data
Ref(2)PGFP-positive puncta in aged indirect flight muscles colocalize with FK2 staining.
“Ref(2)PGFP-positive puncta in aged IFMs tightly colocalize with FK2 staining in IFMGal4>Ref(2)GFP flies”
Quote in the paperNot a substantial claim- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
- Findingown data
Mitochondrial mass decreases in Atg1-overexpressing flies compared with age-matched controls.
“mitochondria mass, indicated by densely dark signals in thick sections of IFMs with Toluidine blue staining[26] (Fig 2C) and mitoGFP (Fig 2D), are progressively decreased in Atg1 OE flies compared with age-matched controls”
Quote in the paperSubstantial claim - Findingown data
Overexpression of Atg1 in indirect flight muscles increases Ref(2)PGFP-positive mitochondria in aged indirect flight muscles compared to controls.
“overexpression of Atg1 renders more Ref(2)PGFP positive mitochondria present in aged IFMs than controls”
Quote in the paperSubstantial claim - Findingown data
Overexpression of pink1 or parkin in indirect flight muscles extends lifespan.
“lifespan was significantly extended in IFMGal4; UASPink1 (median lifespan: 70.8 days, around 7.5% increase) and IFMGal4; UASParkinC2 flies (median:73.5 days, around 11% increase) than controls (median: 65.1 days)”
Quote in the paperSubstantial claim - Findingown data
Ref(2)PGFP-positive puncta in aged indirect flight muscles co-stain with mitochondrial markers.
“Ref(2)PGFP-positive puncta were substantially co-stained with mitochondrial markers, such as an antibody against ETC complex V subunit ATP Synthase (Fig 2A), and a mitochondrial outer membrane targeted mCherry”
Quote in the paperSubstantial claim - Findingown data
Overexpression of pink1 or parkin in indirect flight muscles reduces FK2-positive puncta in aged muscles.
“FK2-positive puncta were significantly reduced in 35-day old muscles of Pink1 overexpressing (Pink1 OE) or Parkin overexpressing (ParkinC2) flies.”
Quote in the paperSubstantial claim- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
- Findingown data
Atg1 knockdown suppresses the rescuing effects of Parkin overexpression on mitochondrial ubiquitylation, ATP level, climbing ability, and lifespan in aged indirect flight muscles.
“Atg1 knock-down substantially block the rescuing effect of Parkin overexpression in aged IFMs in terms of mitochondrial ubiquitylation, ATP level, climbing ability and lifespan”
Quote in the paperSubstantial claim- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
- Interpretationown data
Parkin overexpression promotes mitophagy in aged muscles.
“These results indicated Parkin overexpression promotes mitophagy in aged muscles.”
Quote in the paperSubstantial claim - Premisecitation
Ubiquitinated proteins accumulate in aged Drosophila muscles.
“Recent studies in Drosophila showed that ubiquitinated proteins accumulated in aged muscles[12, 13]”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [12] F Demontis, 2010, FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging, Cell source
Not checked in the free run.
- cites [13] A Rana, 2013, Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan, Proc Natl Acad Sci U S A source
Not checked in the free run.
- Interpretationown data
Atg1 and autophagy are downstream of pink1 and parkin to maintain mitochondrial proteostasis in Drosophila indirect flight muscles.
“Taken together, these results indicate that Atg1 and autophagy are downstream of pink1 and parkin to maintain the mitochondrial proteostasis in Drosophila IFMs.”
Quote in the paperSubstantial claim - Interpretationreasoning
Mitophagy plays a role in the pathogenesis of chronic diseases like Parkinson's disease.
“highlights the role of mitophagy in the pathogenesis of chronic diseases like PD.”
Quote in the paperSubstantial claim - Interpretationown data
Mitophagy of mitochondrial ubiquitination mediated by PINK1/Parkin is crucial for muscle function.
“Our study provides physiological evidence that mitophagy of mitochondrial ubiquitination mediated by PINK1/ Parkin is crucial for muscle function”
Quote in the paperSubstantial claim - Interpretationown data
Augmented Atg1 level is sufficient to induce mitochondrial ubiquitination and subsequent clearance.
“These results demonstrated that an augmented Atg1 level is sufficient to induce mitochondrial ubiquitination and subsequent clearance.”
Quote in the paperSubstantial claim - Premisecitation
A rate-limiting step of mitophagy is degradation of mitochondria in the autolysosome by acidic lysosomes.
“A rate-limiting step of mitophagy is degradation of mitochondria in the autolysosome by acidic lysosomes [4]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [4] G Ashrafi, 2013, The pathways of mitophagy for quality control and clearance of mitochondria, Cell Death Differ source
Not checked in the free run.
- Interpretationown data
Accumulation of ubiquitylated mitochondria is a hallmark of muscle aging in Drosophila.
“These results indicate that accumulation of ubiquitylated mitochondria is a hallmark of muscle aging in Drosophila”
Quote in the paperSubstantial claim- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
- Classified as probably not a substantial claim. 6
- May combine two claims. 5
Classified as probably not a substantial claim.
PremisecitationLoss of pink1 or parkin in Drosophila blocks mitophagy in an age-dependent manner.
“loss of pink1 or parkin in Drosophila block mitophagy in an age-dependent manner[17, 18]”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [17] ES Vincow, 2013, The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo, Proc Natl Acad Sci U S A source
Not checked in the free run.
- cites [18] T Cornelissen, 2018, Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila, Elife source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationMitophagy is an essential process to maintain mitochondrial quality.
“Mitophagy is considered as an essential process to maintain mitochondrial quality [27]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] RJ Youle, 2011, Mechanisms of mitophagy, Nat Rev Mol Cell Biol source
Not checked in the free run.
May combine two claims.
PremisecitationParkin overexpression promotes proteostasis and tissue function of aged muscles in Drosophila and mice.
“Parkin overexpression promotes proteostasis and tissue function of aged muscles both in Drosophila and mice [13, 14]”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [13] A Rana, 2013, Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan, Proc Natl Acad Sci U S A source
Not checked in the free run.
- cites [14] JP Leduc-Gaudet, 2019, Parkin overexpression protects from ageing-related loss of muscle mass and strength, J Physiol source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationATG1/ULK1 is crucial for autophagy initiation.
“ATG1/ULK1 is crucial for autophagy initiation[25]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [25] N. Mizushima, 2010, The role of the Atg1/ULK1 complex in autophagy regulation, Curr Opin Cell Biol source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationRef(2)P is the Drosophila homolog of P62 and can selectively target ubiquitinated proteins for autophagic degradation.
“we introduced Ref(2)P, the Drosophila homolog of P62 [23], which can selectively target ubiquitinated proteins for autophagical degradation [24]”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [23] IP Nezis, 2008, Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain, J Cell Biol source
Not checked in the free run.
- cites [24] C Kraft, 2010, Selective autophagy: ubiquitin-mediated recognition and beyond, Nat Cell Biol source
Not checked in the free run.
May combine two claims.
Interpretationown datapink1/parkin can promote mitochondrial proteostasis, facilitate clearance of damaged mitochondria, and extend lifespan in Drosophila.
“pink1/parkin can promote mitochondrial proteostasis, facilitate clearance of damaged mitochondria, and extend lifespan in Drosophila.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationMitophagy increases with aging, and this age-dependent increase is abolished by loss of Pink1 or parkin in Drosophila.
“studies have shown that mitophagy increases with aging, and this age-dependent increase is abolished by loss of Pink1 or parkin in Drosophila[17, 18]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [17] ES Vincow, 2013, The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo, Proc Natl Acad Sci U S A source
Not checked in the free run.
- cites [18] T Cornelissen, 2018, Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila, Elife source
Not checked in the free run.
May combine two claims.
Interpretationown datapink1/parkin promotes mitophagy of mitochondrial ubiquitination in aged muscles and extends lifespan in an Atg1-dependent manner.
“Taken together, these results show that pink1/parkin promotes mitophagy of mitochondrial ubiquitination in aged muscles and extend lifespan in an Atg1-dependent manner.”
Quote in the paperSubstantial claim- Rests on an assumption: The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationUbiquitination of the mitochondrial outer membrane protein is a prerequisite for autophagosome recruitment via adaptor proteins.
“Ubiquitination of the mitochondrial outer membrane protein is a prerequisite for autophagosome recruitment via adaptor proteins [22]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [22] S Shaid, 2013, Ubiquitination and selective autophagy, Cell Death Differ source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe PINK1/Parkin pathway is among the best characterized pathways through which mitophagy is induced in mammalian cells.
“The PINK1/Parkin) pathway is among the best characterized pathways through which mitophagy is induced in mammalian cells[28]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [28] WX Ding, 2012, Mitophagy: mechanisms, pathophysiological roles, and analysis, Biol Chem source
Not checked in the free run.
The paper relies on this without support.
The FK2 antibody specifically detects ubiquitinated proteins in Drosophila indirect flight muscles.
“FK2 is an antibody against mono and poly-ubiquitinylated protein conjugates.”
The paper relies on this without support.
Mitochondrial homeostasis is maintained by the balance between rejuvenating and damaging events.
“Mitochondrial homeostasis is maintained by the balance between rejuvenating and damaging events.”
The paper relies on this without support.
Cellular ATP is mainly produced in mitochondria by oxidative phosphorylation.
“Cellular ATP is mainly produced in mitochondria by oxidative phosphorylation.”
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?
Boosting mitophagy by overexpressing PINK1, Parkin, DRP1, or p62 in Drosophila muscles improves age-dependent muscle function deterioration and extends lifespan.
“Boosting mitophagy by overexpressing PINK1, Parkin, DRP1, or p62 in Drosophila muscles improves the age-dependent muscle function deterioration and extends lifespan [214, 236, 237].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [236]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
ATP assay thorax counts disagree
MinorThe methods specify five thoraces for each ATP measurement, whereas the Figure 3 legend specifies six thoraces for ATP normalization.
“For each measurement, 5 thoraces were freshly dissected and immediately homogenized in 50 μl lysis buffer.”
“ATP level was normalized with protein level from six thoraces, and triplicates was tested for each genotype.”
Cites
Repertoires 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
Youle, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273 · 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
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
The pathways of mitophagy for quality control and clearance of mitochondria
Ashrafi, G., & Schwarz, T. L. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.81 · Cited by 1,900 · see citing works
Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
Clark, I. E., Dodson, M. W., Jiang, C., Cao, J. H., Huh, J. R., Seol, J. H., Yoo, S. J., Hay, B. A., & Guo, M. (2006) · Nature · doi:10.1038/nature04779 · Cited by 1,788 · see citing works
Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
Park, J., Lee, S. B., Lee, S., Kim, Y., Song, S., Kim, S., Bae, E., Kim, J., Shong, M., Kim, J.-M., et al. (2006) · Nature · doi:10.1038/nature04788 · Cited by 1,705 · see citing works
The mitochondrial basis of aging
Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441 · see citing works
The role of the Atg1/ULK1 complex in autophagy regulation
Mizushima, N. (2010) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.12.004 · Cited by 1,062 · 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
Ubiquitination and selective autophagy
Shaid, S., Brandts, C. H., Serve, H., & Dikic, I. (2013) · Cell Death & Differentiation · doi:10.1038/cdd.2012.72 · Cited by 800 · 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
Deng, H., Dodson, M. W., Huang, H., & Guo, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803998105 · Cited by 683 · see citing works
Self-citationFOXO/4E-BP Signaling in Drosophila Muscles Regulates Organism-wide Proteostasis during Aging
Demontis, F., & Perrimon, N. (2010) · Cell · doi:10.1016/j.cell.2010.10.007 · Cited by 656 · see citing works
Selective autophagy: ubiquitin-mediated recognition and beyond
Kraft, C., Peter, M., & Hofmann, K. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-836 · Cited by 639 · see citing works
Quality control of mitochondria: protection against neurodegeneration and ageing
Tatsuta, T., & Langer, T. (2008) · The EMBO Journal · doi:10.1038/sj.emboj.7601972 · Cited by 519 · see citing works
Loss-of-Function of Human PINK1 Results in Mitochondrial Pathology and Can Be Rescued by Parkin
Exner, N., Treske, B., Paquet, D., Holmström, K. M., Schiesling, C., Gispert, S., Carballo‐Carbajal, I., Berg, D., Hoepken, H.-H., Gasser, T., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0719-07.2007 · Cited by 511 · see citing works
The 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
Nezis, I. P., Simonsen, A., Sagona, A. P., Finley, K., Gaumer, S., Contamine, D., Rusten, T. E., Stenmark, H., & Brech, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200711108 · Cited by 370 · see citing works
Rana, A., Rera, M., & Walker, D. W. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216197110 · Cited by 335 · 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
Sterky, F. H., Lee, S., Wibom, R., Olson, L., & Larsson, N. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1103295108 · Cited by 296 · see citing works
Rana, A., Oliveira, M. P., Khamoui, A. V., Aparicio, R., Rera, M., Rossiter, H. B., & Walker, D. W. (2017) · Nature Communications · doi:10.1038/s41467-017-00525-4 · Cited by 294 · see citing works
Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila
Cornelissen, T., Vilain, S., Vints, K., Gounko, N., Verstreken, P., & Vandenberghe, W. (2018) · eLife · doi:10.7554/elife.35878 · Cited by 239 · see citing works
Chinnery, P. F., Samuels, D. C., Elson, J. L., & Turnbull, D. M. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11310-9 · Cited by 234 · see citing works
PINK1-induced mitophagy promotes neuroprotection in Huntington’s disease
Khalil, B., Fissi, N. E., Aouane, A., Cabirol-Pol, M.-J., Rival, T., & Liévens, J.-C. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.581 · Cited by 228 · see citing works
Aparicio, R., Rana, A., & Walker, D. W. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.070 · Cited by 129 · see citing works
Parkin overexpression protects from ageing‐related loss of muscle mass and strength
Leduc‐Gaudet, J., Reynaud, O., Hussain, S. N., & Gouspillou, G. (2019) · The Journal of Physiology · doi:10.1113/jp277157 · Cited by 119 · see citing works
Drosophila Porin/VDAC Affects Mitochondrial Morphology
Park, J., Kim, Y., Choi, S., Koh, H., Lee, S., Kim, J., & Chung, J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013151 · Cited by 55 · see citing works
Todd, A. M., & Staveley, B. E. (2012) · Genetics and Molecular Research · doi:10.4238/2012.may.21.6 · Cited by 46 · see citing works
Ma, P., Yun, J., Deng, H., & Guo, M. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e18-04-0243 · Cited by 37 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- P Ma, 2018, Atg1 mediated autophagy suppresses tissue degeneration in pink1/parkin mutants by promoting mitochondrial fission in Drosophila, Mol Biol Cell
Cited by
Sorted by citations
Romanello, V., & Sandri, M. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03662-0 · Cited by 197 · see citing works
Mitophagy and Oxidative Stress: The Role of Aging
Gaetano, A. D., Gibellini, L., Zanini, G., Nasi, M., Cossarizza, A., & Pinti, M. (2021) · Antioxidants · doi:10.3390/antiox10050794 · Cited by 188 · see citing works
The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia
Romanello, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010091 · Cited by 101 · see citing works
Mitophagy in aging and longevity
Guo, J., & Chiang, W. (2021) · IUBMB Life · doi:10.1002/iub.2585 · Cited by 58 · see citing works
Reversible mitophagy drives metabolic suppression in diapausing beetles
Lebenzon, J. E., Denezis, P. W., Mohammad, L., Mathers, K. E., Turnbull, K. F., Staples, J. F., & Sinclair, B. J. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2201089119 · Cited by 50 · see citing works
Ubiquitin Ligases in Longevity and Aging Skeletal Muscle
Hughes, D. C., Baehr, L. M., Waddell, D. S., Sharples, A. P., & Bodine, S. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147602 · Cited by 45 · see citing works
Wang, X., Qi, L., Cheng, Y.-F., Ji, X., Chi, T., Liu, P., & Zou, L. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00810-5 · Cited by 43 · see citing works
Role of the mtDNA Mutations and Mitophagy in Inflammaging
Dabravolski, S. A., Nikiforov, N. G., Zhuravlev, A. D., Orekhov, N. A., Grechko, A. V., & Orekhov, A. N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031323 · Cited by 38 · see citing works
Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson’s Disease
Prasuhn, J., & Brüggemann, N. (2021) · Genes · doi:10.3390/genes12111840 · Cited by 34 · see citing works
Human Rights Here and Now: Celebrating the Universal Declaration of Human Rights.
Flowers, N. B. (1998) · Cited by 31 · see citing works
Proteostasis-associated aging: lessons from a Drosophila model
Yu, G., & Hyun, S. (2020) · Genes & Genomics · doi:10.1007/s13258-020-01012-9 · Cited by 29 · see citing works
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Leduc‐Gaudet, J., Hussain, S. N. A., & Gouspillou, G. (2022) · The Journal of Physiology · doi:10.1113/jp282567 · Cited by 26 · see citing works
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Daskalaki, I., & Tavernarakis, N. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111345 · Cited by 18 · see citing works
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Leo, V. D., Gomes, T. M. B., & Vincent, A. E. (2023) · Biochemical Journal · doi:10.1042/bcj20220233 · Cited by 18 · see citing works
Jiang, M., Lai, X., Zhang, Y., Shen, M., Ma, H., Liu, A., Wu, J., & Yan, J. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/6568748 · Cited by 17 · see citing works
Miller, S. J., Darji, R. Y., Walaieh, S., Lewis, J. A., & Logan, R. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1271941 · Cited by 16 · see citing works
Bypassing mitochondrial defects rescues Huntington's phenotypes in Drosophila
Campesan, S., Popolo, I. D., Marcou, K., Straatman-Iwanowska, A. A., Repici, M., Boytcheva, K. V., Cotton, V. E., Allcock, N., Rosato, E., Kyriacou, C. P., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106236 · Cited by 14 · see citing works
Markers and mechanisms of death in Drosophila
Tower, J. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1292040 · Cited by 13 · see citing works
Age-related tolerance to paraquat-induced parkinsonism in Drosophila melanogaster
Neves, P. F. R., Milanesi, B. B., Paz, L. V., Monteiro, V. A. C. D. M., Neves, L. T., da Veiga, L. C., da Silva, R. B., Sulzbach, J. H., Knijkik, G. P., Ribeiro, E. C. D. R., et al. (2022) · Toxicology Letters · doi:10.1016/j.toxlet.2022.03.010 · Cited by 13 · see citing works
Wen, D., Gao, Y., Wang, J., Wang, S., Zhong, Q., & Hou, W.-Q. (2023) · Genes & Nutrition · doi:10.1186/s12263-023-00725-2 · Cited by 12 · see citing works
Self-citationChen, Q., Huang, W., Çapanoğlu, E., Amrouche, A. T., & Lu, B. (2023) · Food Frontiers · doi:10.1002/fft2.261 · Cited by 12 · see citing works
Reynaud, O., Wang, J. P., Ayoub, M., Leduc‐Gaudet, J., Mayaki, D., Dulac, M., Hussain, S. N. A., Bergeron, R., & Gouspillou, G. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00388.2022 · Cited by 9 · see citing works
Mitochondrial homeostasis in stem cell senescence
Peng, B., & Zhang, H. (2025) · Oral Science and Homeostatic Medicine · doi:10.26599/oshm.2025.9610006 · Cited by 8 · see citing works
Du, X., Wang, Y., Wang, J., Liu, X., Chen, J., Kang, J., Yang, X., & Wang, H. (2022) · Experimental Gerontology · doi:10.1016/j.exger.2022.111856 · Cited by 8 · see citing works
Targeting ATAD3A Phosphorylation Mediated by TBK1 Ameliorates Senescence‐Associated Pathologies
He, Y., Liu, Y., Zheng, M., Zou, Y., Huang, M., Wang, L., Gao, G., Zhou, Z., & Jin, G. (2024) · Advanced Science · doi:10.1002/advs.202404109 · Cited by 7 · see citing works
Komlós, M., Szinyákovics, J., Falcsik, G., Sigmond, T., Jezsó, B., Vellai, T., & Kovács, T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098100 · Cited by 7 · see citing works
Liu, H., Das, P. P., Zhang, J., Yu, L., Wang, M., Lin, Q., Zhou, Y., Xu, Q., & Wong, S. (2021) · Journal of Proteomics · doi:10.1016/j.jprot.2021.104314 · Cited by 7 · see citing works
Sheng, Y., Zhu, X., Wei, L., Zou, Y., Qi, X., Shi, R., Xu, W., Wang, X., Ding, G., & Duan, Y. (2024) · Aging · doi:10.18632/aging.205748 · Cited by 6 · see citing works
Xue, J., Li, G., Ji, X., Liu, Z. H., Wang, H. L., & Xiao, G. (2022) · Journal of Neurochemistry · doi:10.1111/jnc.15574 · Cited by 5 · see citing works
Matamoros, A., Soffia, J. P., Munoz, M. H., Maturana, M., Rangel-Ramírez, M. A., Gonzalez-Ibañez, A. M., Gómez-Lillo, G., Astorga, C., Ruíz, L. M., Jorquera, R. A., et al. (2026) · Aging Cell · doi:10.1111/acel.70508 · Cited by 4 · see citing works
Ma, H., Guo, Z., Gai, C., Cheng, C., Zhang, J., Zhang, Y., Yang, L., Feng, W.-D., Gao, Y., & Sun, H. (2020) · Journal of Traditional Chinese Medical Sciences · doi:10.1016/j.jtcms.2020.07.007 · Cited by 4 · see citing works
Mitophagy in sarcopenic muscle and practical recommendations for exercise training
Sanchez, A. M. J., & Solsona, R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822146-4.00011-9 · Cited by 1 · see citing works
Parkin overexpression modulates gut-microbiota composition during aging in Drosophila melanogaster
Sârghie, L., Istvan, P., Aparicio, R., Walker, D. W., Tăcutu, R., & Surleac, M. D. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1672083
Reynaud, O., Ayoub, M., Leduc‐Gaudet, J., Cefis, M., Lussier, M. P., Hussain, S. N. A., & Gouspillou, G. (2026) · Scientific Reports · doi:10.1038/s41598-025-34223-9
Álvarez‐Luquín, D. D., González-Fernández, R. R., Ichikawa-Escamilla, E., Torres-Velasco, M. E., Martínez-Martínez, E. J., Arce-Sillas, A., Juárez-Vaquera, V. H., Miranda-Narváez, C. L., Hernández, M., & Adalid-Peralta, L. V. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115764
- Authors
- Si, H., Ma, P., Liang, Q., Yin, Y., Wang, P., Zhang, Q., Wang, S., & Deng, H.
- Affiliations
- Guangxi University (CN)
- Tongji University (CN)
- Corresponding author
- Deng, Hansong
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-11-12
- Volume
- 14
- Issue
- 11
- Pages
- e0225214
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6850535
- OpenAlex
- W2987428619
- Semantic Scholar
- bf4be65269889301b8946291a69cf2818b296db4
- Cited by
- 37
- References
- 31
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 5
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Basic Research Program of China (2018YFA0107100)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- PINK1, Parkin, mitophagy, mitochondrial ubiquitination, mitochondrial proteostasis, indirect flight muscle, lifespan extension, aging, autophagy, Atg1, ATP levels, Parkinson's disease, Drosophila melanogaster
- MeSH terms
- Adenosine Triphosphate, Animals, Autophagy, Drosophila melanogaster, Humans, Mitochondria, Gene Expression, Muscle, Skeletal, Drosophila Proteins, Animals, Genetically Modified, Ubiquitin-Protein Ligases, Ubiquitination
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
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.
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