Articles by Jonathan M. Memme in JoVE
Application of Chronic Stimulation to Study Contractile Activity-induced Rat Skeletal Muscle Phenotypic Adaptations Yuho Kim1,2,3, Jonathan M. Memme1,2, David A. Hood1,2 1Muscle Health Research Centre, York University, 2School of Kinesiology and Health Science, York University, 3National Heart, Lung, and Blood Institute, National Institutes of Health This protocol describes the use of the chronic contractile activity model of exercise to observe stimulation-induced skeletal muscle adaptations in the rat hindlimb.
Other articles by Jonathan M. Memme on PubMed
Recent Advances in Mitochondrial Turnover During Chronic Muscle Disuse Integrative Medicine Research. Dec, 2014 | Pubmed ID: 28664093 Chronic muscle disuse, such as that resulting from immobilization, denervation, or prolonged physical inactivity, produces atrophy and a loss of mitochondria, yet the molecular relationship between these events is not fully understood. In this review we attempt to identify the key regulatory steps mediating the loss of muscle mass and the decline in mitochondrial content and function. An understanding of common intracellular signaling pathways may provide much-needed insight into the possible therapeutic targets for treatments that will maintain aerobic energy metabolism and preserve muscle mass during disuse conditions.
Chronology of UPR Activation in Skeletal Muscle Adaptations to Chronic Contractile Activity American Journal of Physiology. Cell Physiology. Jun, 2016 | Pubmed ID: 27122157 The mitochondrial and endoplasmic reticulum unfolded protein responses (UPR(mt) and UPR(ER)) are important for cellular homeostasis during stimulus-induced increases in protein synthesis. Exercise triggers the synthesis of mitochondrial proteins, regulated in part by peroxisome proliferator activator receptor-γ coactivator 1α (PGC-1α). To investigate the role of the UPR in exercise-induced adaptations, we subjected rats to 3 h of chronic contractile activity (CCA) for 1, 2, 3, 5, or 7 days followed by 3 h of recovery. Mitochondrial biogenesis signaling, through PGC-1α mRNA, increased 14-fold after 1 day of CCA. This resulted in 10-32% increases in cytochrome c oxidase activity, indicative of mitochondrial content, between days 3 and 7, as well as increases in the autophagic degradation of p62 and microtubule-associated proteins 1A/1B light chain 3A (LC3)-II protein. Before these adaptations, the UPR(ER) transcripts activating transcription factor-4, spliced X-box-binding protein 1, and binding immunoglobulin protein were elevated (1.3- to 3.8-fold) at days 1-3, while CCAAT/enhancer-binding protein homologous protein (CHOP) and chaperones binding immunoglobulin protein and heat shock protein (HSP) 70 were elevated at mRNA and protein levels (1.5- to 3.9-fold) at days 1-7 of CCA. The mitochondrial chaperones 10-kDa chaperonin, HSP60, and 75-kDa mitochondrial HSP, the protease ATP-dependent Clp protease proteolytic subunit, and the regulatory protein sirtuin-3 of the UPR(mt) were concurrently induced 10-80% between days 1 and 7 To test the role of the UPR in CCA-induced remodeling, we treated animals with the endoplasmic reticulum stress suppressor tauroursodeoxycholic acid and subjected them to 2 or 7 days of CCA. Tauroursodeoxycholic acid attenuated CHOP and HSP70 protein induction; however, this failed to impact mitochondrial remodeling. Our data indicate that signaling to the UPR is rapidly activated following acute contractile activity, that this is attenuated with repeated bouts, and that the UPR is involved in chronic adaptations to CCA; however, this appears to be independent of CHOP signaling.
Function of Specialized Regulatory Proteins and Signaling Pathways in Exercise-induced Muscle Mitochondrial Biogenesis Integrative Medicine Research. Sep, 2016 | Pubmed ID: 28462117 Skeletal muscle mitochondrial content and function are regulated by a number of specialized molecular pathways that remain to be fully defined. Although a number of proteins have been identified to be important for the maintenance of mitochondria in quiescent muscle, the requirement for these appears to decrease with the activation of multiple overlapping signaling events that are triggered by exercise. This makes exercise a valuable therapeutic tool for the treatment of mitochondrially based metabolic disorders. In this review, we summarize some of the traditional and more recently appreciated pathways that are involved in mitochondrial biogenesis in muscle, particularly during exercise.