HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Kim, H-J; Nagano, Y; Choi, SJ; Park, SY; Kim, H; Yao, T-P; Lee, J-Y
Published Date
- September 4, 2015
Published In
Volume / Issue
- 464 / 4
Start / End Page
- 1235 - 1240
PubMed ID
- 26210454
Electronic International Standard Serial Number (EISSN)
- 1090-2104
Digital Object Identifier (DOI)
- 10.1016/j.bbrc.2015.07.111
Language
- eng
Conference Location
- United States