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Ulk1 is Required for Lysosome Targeting to Damaged Mitochondria Following Acute Exercise
Author(s) -
Laker Rhianna,
Lira Vitor,
Wilson Rebecca,
Zhang Mei,
Yan Zhen
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.821.9
Subject(s) - mitophagy , autophagy , skeletal muscle , lysosome , ulk1 , microbiology and biotechnology , lamp1 , mitochondrion , chemistry , biology , phosphorylation , endocrinology , protein kinase a , biochemistry , apoptosis , ampk , enzyme
Mitochondrial health is critical for skeletal muscle function and is improved by exercise training. Using our newly developed mitochondrial reporter gene, pMitoTimer , with somatic gene transfer in mouse flexor digitorum brevis (FDB) muscle, we observed a transient increase of mitochondrial stress following an acute bout of treadmill running (peak at 6 hrs post exercise). This was accompanied by increased mitophagy as shown by co‐localization of lysosome associated membrane protein 1 (Lamp1)‐YFP with MitoTimer. We also observed increased phosphorylation of unc‐51 like autophagy activating kinase 1 (Ulk1) at serine 555 (S555) immediately after exercise suggesting its activation. To determine the role of Ulk1 in exercise‐induced mitophagy, we co‐transfected the FDB muscle with pMitoTimer and pLamp1‐YFP in muscle‐specific Ulk1 knockout mice (MKO). Compared with WT mice, MKO mice had similar levels of Lamp1‐positive puncta, but they did not co‐localize with MitoTimer. WT and MKO mice had increased Lamp1 puncta following exercise, but in MKO mice the signals did not co‐localize with MitoTimer either. These findings suggest that an acute bout of exercise induces a transient increase in mitophagy in skeletal muscle. In addition, our observations in MKO mice suggest that targeting of lysosome to the stressed/damaged mitochondria is dependent on Ulk1. This signaling pathway may play an important role in exercise training‐induced mitochondrial quality control in skeletal muscle. Supported by NIH grant R01AR050429