{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nichenko AS"],"funding":["HHS | National Institutes of Health","NIAMS NIH HHS"],"pagination":["C242-C252"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7052610"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["318(2)"],"pubmed_abstract":["The objective of this study was to interrogate the link between mitochondrial dysfunction and mitochondrial-specific autophagy in skeletal muscle. C57BL/6J mice were used to establish a time course of mitochondrial function and autophagy induction after fatigue (<i>n</i> = 12), eccentric contraction-induced injury (<i>n</i> = 20), or traumatic freeze injury (FI, <i>n</i> = 28); only FI resulted in a combination of mitochondrial dysfunction, i.e., decreased mitochondrial respiration, and autophagy induction. Moving forward, we tested the hypothesis that mitochondrial-specific autophagy is important for the timely recovery of mitochondrial function after FI. Following FI, there is a significant increase in several mitochondrial-specific autophagy-related protein contents including dynamin-related protein 1 (Drp1), BCL1 interacting protein (BNIP3), Pink1, and Parkin (~2-fold, <i>P</i> < 0.02). Also, mitochondrial-enriched fractions from FI muscles showed microtubule-associated protein light chain B1 (LC3)II colocalization suggesting autophagosome assembly around the damaged mitochondrial. Unc-51 like autophagy activating kinase (Ulk1) is considered necessary for mitochondrial-specific autophagy and herein we utilized a mouse model with Ulk1 deficiency in adult skeletal muscle (<i>myogenin-Cre</i>). While Ulk1 knockouts had contractile weakness compared with littermate controls (-27%, <i>P</i> < 0.02), the recovery of mitochondrial function was not different, and this may be due in part to a partial rescue of Ulk1 protein content within the regenerating muscle tissue of knockouts from differentiated satellite cells in which Ulk1 was not genetically altered via <i>myogenin-Cre</i>. Lastly, autophagy flux was significantly less in injured versus uninjured muscles (-26%, <i>P</i> < 0.02) despite the increase in autophagy-related protein content. This suggests autophagy flux is not upregulated to match increases in autophagy machinery after injury and represents a potential bottleneck in the clearance of damaged mitochondria by autophagy."],"journal":["American journal of physiology. Cell physiology"],"pubmed_title":["Mitochondrial-specific autophagy linked to mitochondrial dysfunction following traumatic freeze injury in mice."],"pmcid":["PMC7052610"],"funding_grant_id":["R01 AR070178","T32 AR007612","1R01AR070178"],"pubmed_authors":["Qualls AE","Yin H","Call JA","Nichenko AS","Southern WM","Tehrani KF","Flemington AB","Yin A","Mortensen LJ","Mercer GH"],"additional_accession":[]},"is_claimable":false,"name":"Mitochondrial-specific autophagy linked to mitochondrial dysfunction following traumatic freeze injury in mice.","description":"The objective of this study was to interrogate the link between mitochondrial dysfunction and mitochondrial-specific autophagy in skeletal muscle. C57BL/6J mice were used to establish a time course of mitochondrial function and autophagy induction after fatigue (<i>n</i> = 12), eccentric contraction-induced injury (<i>n</i> = 20), or traumatic freeze injury (FI, <i>n</i> = 28); only FI resulted in a combination of mitochondrial dysfunction, i.e., decreased mitochondrial respiration, and autophagy induction. Moving forward, we tested the hypothesis that mitochondrial-specific autophagy is important for the timely recovery of mitochondrial function after FI. Following FI, there is a significant increase in several mitochondrial-specific autophagy-related protein contents including dynamin-related protein 1 (Drp1), BCL1 interacting protein (BNIP3), Pink1, and Parkin (~2-fold, <i>P</i> < 0.02). Also, mitochondrial-enriched fractions from FI muscles showed microtubule-associated protein light chain B1 (LC3)II colocalization suggesting autophagosome assembly around the damaged mitochondrial. Unc-51 like autophagy activating kinase (Ulk1) is considered necessary for mitochondrial-specific autophagy and herein we utilized a mouse model with Ulk1 deficiency in adult skeletal muscle (<i>myogenin-Cre</i>). While Ulk1 knockouts had contractile weakness compared with littermate controls (-27%, <i>P</i> < 0.02), the recovery of mitochondrial function was not different, and this may be due in part to a partial rescue of Ulk1 protein content within the regenerating muscle tissue of knockouts from differentiated satellite cells in which Ulk1 was not genetically altered via <i>myogenin-Cre</i>. Lastly, autophagy flux was significantly less in injured versus uninjured muscles (-26%, <i>P</i> < 0.02) despite the increase in autophagy-related protein content. This suggests autophagy flux is not upregulated to match increases in autophagy machinery after injury and represents a potential bottleneck in the clearance of damaged mitochondria by autophagy.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Feb","modification":"2025-04-25T20:04:07.269Z","creation":"2025-04-06T08:08:59.442Z"},"accession":"S-EPMC7052610","cross_references":{"pubmed":["31721614"],"doi":["10.1152/ajpcell.00123.2019"]}}