The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.
Parkin is required for exercise-induced mitophagy in muscle: impact of aging
Abstract
The maintenance of muscle health with advancing age is dependent on mitochondrial homeostasis. While reductions in mitochondrial biogenesis have been observed with age, less is known regarding organelle degradation. Parkin is an E3 ubiquitin ligase implicated in mitophagy, but few studies have examined Parkin’s contribution to mitochondrial turnover in muscle. Wild-type (WT) and Parkin knockout (KO) mice were used to delineate a role for Parkin-mediated mitochondrial degradation in aged muscle, in concurrence with exercise. Aged animals exhibited declines in muscle mass and mitochondrial content, paralleled by a nuclear environment endorsing the transcriptional repression of mitochondrial biogenesis. Mitophagic signaling was enhanced following acute endurance exercise in young WT mice but was abolished in the absence of Parkin. Basal mitophagy flux of the autophagosomal protein lipidated microtubule-associated protein 1A/1B-light chain 3 was augmented in aged animals but did not increase additionally with exercise when compared with young animals. In the absence of Parkin, exercise increased the nuclear localization of Parkin-interacting substrate, corresponding to a decrease in nuclear peroxisome proliferator gamma coactivator-1α. Remarkably, exercise enhanced mitochondrial ubiquitination in both young WT and KO animals. This suggested compensation of alternative ubiquitin ligases that were, however, unable to restore the diminished exercise-induced mitophagy in KO mice. Under basal conditions, we demonstrated that Parkin was required for mitochondrial mitofusin-2 ubiquitination. We also observed an abrogation of exercise-induced mitophagy in aged muscle. Our results demonstrate that acute exercise-induced mitophagy is dependent on Parkin and attenuated with age, which likely contributes to changes in mitochondrial content and quality in aging muscle.
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In the citing paper
“Although conflicting data exist [54,145,146,147], several studies reported that mitophagy-related proteins are decreased in the skeletal muscle of old rodents [46,120,148,149,150,151,152].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [147]
In the citing paper
“We and others have reported that muscles of Parkin-deficient mice display several aging-like features, including contractile dysfunction [154] and impaired mitochondrial energetics [147,153,154,155].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [147]
In the citing paper
“Importantly, the majority of studies that reported an increase in Parkin content in aged muscles also reported that mitophagy was impaired/insufficient in aged skeletal muscles [145,146,147].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [147]
In the citing paper
“For instance, it has been reported that muscles from Parkin-deficient mice display lower mitophagy flux in response to acute exercise [147] and endurance training [153].”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [147]
In the citing paper
“Under the conditions of stress, injury or aging, mitochondrial kinase PINK1 can gather outside the membrane of dysfunctional mitochondria and translocate them into it selectively by phosphorylating and recruiting Parkin, and then ubiquitinate outer mitochondrial membrane proteins such as mitochondrial fusion key proteins Mfn1/2 and fission key protein Drp1 to participate in mitophagy [48].”
From Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway (2021) · cites this paper as [48]
Citations
Cites
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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
Mitochondrial Fission, Fusion, and Stress
Youle, R. J., & van der Bliek, A. M. (2012) · Science · doi:10.1126/science.1219855 · Cited by 3,674
TFEB Links Autophagy to Lysosomal Biogenesis
Settembre, C., Di Malta, C., Polito, V. A., Arencibia, M. G., Vetrini, F., Erdin, S., Erdin, S. U., Huynh, T., Medina, D., Colella, P., et al. (2011) · Science · doi:10.1126/science.1204592 · Cited by 3,365
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Janssen, I., Heymsfield, S. B., & Ross, R. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50216.x · Cited by 3,139
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
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
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
A Gene Network Regulating Lysosomal Biogenesis and Function
Sardiello, M., Palmieri, M., di Ronza, A., Medina, D. L., Valenza, M., Gennarino, V. A., Di Malta, C., Donaudy, F., Embrione, V., Polishchuk, R. S., et al. (2009) · Science · doi:10.1126/science.1174447 · Cited by 2,543
Cited by
Sorted by citations
Maintenance of Skeletal Muscle Mitochondria in Health, Exercise, and Aging
Hood, D. A., Memme, J. M., Oliveira, A. N., & Triolo, M. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114310 · Cited by 567
Self-citationMitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging
Jiménez‐Loygorri, J. I., Villarejo‐Zori, B., Viedma-Poyatos, Á., Zapata‐Muñoz, J., Benítez‐Fernández, R., Frutos-Lisón, M. D., Tomás-Barberán, F. A., Espı́n, J. C., Área-Gómez, E., Gómez-Durán, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45044-1 · Cited by 394
Exercise and mitochondrial health
Memme, J. M., Erlich, A. T., Phukan, G., & Hood, D. A. (2021) · The Journal of Physiology · doi:10.1113/jp278853 · Cited by 343
Self-citationSkeletal muscle mitochondrial remodeling in exercise and diseases
Gan, Z., Fu, T., Kelly, D. P., & Vega, R. B. (2018) · Cell Research · doi:10.1038/s41422-018-0078-7 · Cited by 297
Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
Leduc-Gaudet, J.-P., Hussain, S. N. A., Barreiro, E., & Gouspillou, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158179 · Cited by 268
“For instance, it has been reported that muscles from Parkin-deficient mice display lower mitophagy flux in response to acute exercise [147] and endurance traini g [153].”
Background
Metadata
- Authors
- Chen, C. C. W., Erlich, A. T., Crilly, M. J., & Hood, D. A.
- Affiliations
- York University (CA)
- Corresponding author
- Hood, David A.
- ORCID
- Hood, David A.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2018-09-01
- Volume
- 315
- Issue
- 3
- Pages
- E404-E415
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2807114871
- Semantic Scholar
- 4601835e866b1f7b1dd68edc05405eb6f445e786
- Cited by
- 108
- References
- 67
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 13 · 2023: 14 · 2022: 19 · 2021: 19 · 2020: 11 · 2019: 7 · 2018: 5
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
- Canada Research Chairs (Chaires de recherche du Canada)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- Parkin, mitophagy, physical activity, muscle aging, mitochondrial homeostasis, mitochondrial biogenesis, PGC-1α, mitofusin 2, mitochondrial ubiquitination, E3 ubiquitin ligase, skeletal muscle, autophagy
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Aging, Animals, Electron Transport Complex IV, Mice, Inbred C57BL, Mitochondria, Muscle, Physical Conditioning, Animal, Repressor Proteins, Mice, Knockout, Muscle, Skeletal, GTP Phosphohydrolases, Ubiquitin-Protein Ligases, Mice, Ubiquitination, Mitophagy
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