HDAC6 maintains mitochondrial connectivity under hypoxic stress by suppressing MARCH5/MITOL dependent MFN2 degradation.

Published

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 2015

Published In

Volume / Issue

  • 464 / 4

Start / End Page

  • 1235 - 1240

PubMed ID

  • 26210454

Pubmed Central ID

  • 26210454

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2015.07.111

Language

  • eng