The Role of Parkin-Mediated Mitophagy During Aging and Exercise in Skeletal Muscle

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dc.contributor.advisorHood, David A.
dc.creatorChen, Chris Chin Wah
dc.date.accessioned2018-05-28T12:58:21Z
dc.date.available2018-05-28T12:58:21Z
dc.date.copyright2018-02-05
dc.date.issued2018-05-28
dc.date.updated2018-05-28T12:58:21Z
dc.degree.disciplineKinesiology & Health Science
dc.degree.levelDoctoral
dc.degree.namePhD - Doctor of Philosophy
dc.description.abstractMitochondria are double membrane-bound organelles that play a significant role in producing energy for the cell, as well as mediating an array of metabolic pathways. Long-lived mitochondria that are unable to sustain the energetic requirements of the cell are targeted for lysosomal degradation through a process termed mitophagy. Parkin is a ubiquitin ligase that is involved in mitophagy and the turnover of mitochondria. Parkin is extensively studied in neuronal tissue, but its role in skeletal muscle has not been fully explored. The overall purpose of this dissertation was to examine the effects of aging and exercise on Parkin-mediated mitophagy in skeletal muscle. We first investigated the role of Parkin in the regulation of mitophagy during exercise in young and old muscle. To do this, we subjected young and aged groups of wild-type (WT) and Parkin knockout (KO) mice to an acute bout of endurance exercise. We found a robust exercise-induced rise in mitophagy flux in young WT animals, but did not observe this in the absence of Parkin. Basal mitophagy flux was elevated in aged animals, but this did not increase additionally with exercise. We also noted a reduced transcriptional drive towards mitochondrial biogenesis in KO and aged animals. The results demonstrate that acute exercise can selectively increase mitochondrial targeting for degradation, and that this process is dependent on Parkin, as well as with age. We next focused on the role of Parkin in mitochondrial turnover with endurance training. We found that mitophagy flux did not increase with training, but that flux lessened with a subsequent bout of acute exercise. This exercise-induced adaptation was not observed in trained KO animals. Our data indicate that exercise-induced mitochondrial biogenesis diminishes Parkin-mediated mitophagy as an adaptive response to repeated bouts of exercise. The significance of this research is that we have indicated a role for Parkin in maintaining mitochondrial turnover, and show that Parkin can facilitate mitophagy, dependent on organelle content and quality in skeletal muscle.
dc.identifier.urihttp://hdl.handle.net/10315/34562
dc.language.isoen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectPhysiology
dc.subject.keywordsMitochondria
dc.subject.keywordsAging
dc.subject.keywordsExercise
dc.subject.keywordsParkin
dc.subject.keywordsMitophagy
dc.subject.keywordsAutophagy
dc.subject.keywordsMitochondrial biogenesis
dc.subject.keywordsPGC-1alpha
dc.subject.keywordsPARIS
dc.subject.keywordsCOX
dc.subject.keywordsMuscle plasticity
dc.subject.keywordsMetabolism
dc.subject.keywordsEndurance training
dc.subject.keywordsPhysiology
dc.subject.keywordsAdaptation
dc.titleThe Role of Parkin-Mediated Mitophagy During Aging and Exercise in Skeletal Muscle
dc.typeElectronic Thesis or Dissertation

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