Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10749928 | Biochemical and Biophysical Research Communications | 2015 | 23 Pages |
Abstract
Mitochondria undergo fusion and fission in response to various metabolic stresses. Growing evidences have suggested that the morphological change of mitochondria by fusion and fission plays a critical role in protecting mitochondria from metabolic stresses. Here, we showed that hypoxia treatment could induce interaction between HDAC6 and MFN2, thus protecting mitochondrial connectivity. Mechanistically, we demonstrated that a mitochondrial ubiquitin ligase MARCH5/MITOL was responsible for hypoxia-induced MFN2 degradation in HDAC6 deficient cells. Notably, genetic abolition of HDAC6 in amyotrophic lateral sclerosis model mice showed MFN2 degradation with MARCH5 induction. Our results indicate that HDAC6 is a critical regulator of MFN2 degradation by MARCH5, thus protecting mitochondrial connectivity from hypoxic stress.
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Authors
Hak-June Kim, Yoshito Nagano, Su Jin Choi, Song Yi Park, Hongtae Kim, Tso-Pang Yao, Joo-Yong Lee,