Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology

Cuilin Zhang, Zhun Shi, Lingzhi Zhang, Zehua Zhou, Xiaoyuan Zheng, Guiying Liu, Guojun Bu, Paul E. Fraser, Huaxi Xu, Yun Wu Zhang

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Mitochondrial morphology is regulated by fusion and fission machinery. Impaired mitochondria dynamics cause various diseases, including Alzheimer's disease. Appoptosin (encoded by SLC25A38) is a mitochondrial carrier protein that is located in the mitochondrial inner membrane. Appoptosin overexpression causes overproduction of reactive oxygen species (ROS) and caspasedependent apoptosis, whereas appoptosin downregulation abolishes β-amyloid-induced mitochondrial fragmentation and neuronal death during Alzheimer's disease. Herein, we found that overexpression of appoptosin resulted in mitochondrial fragmentation in a manner independent of its carrier function, ROS production or caspase activation. Although appoptosin did not affect levels of mitochondrial outer-membrane fusion (MFN1 and MFN2), inner-membrane fusion (OPA1) and fission [DRP1 (also known as DNM1L) and FIS1] proteins, appoptosin interacted with MFN1 and MFN2, as well as with the mitochondrial ubiquitin ligase MITOL (also known as MARCH5) but not OPA1, FIS1 or DRP1. Appoptosin overexpression impaired the interaction between MFN1 and MFN2, and mitochondrial fusion. By contrast, co-expression of MFN1, MITOL and a dominant-negative form of DRP1, DRP1K38A, partially rescued appoptosin-induced mitochondrial fragmentation and apoptosis, whereas co-expression of FIS1 aggravated appoptosin-induced apoptosis. Together, our results demonstrate that appoptosin can interact with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology.

Original languageEnglish (US)
Pages (from-to)994-1002
Number of pages9
JournalJournal of cell science
Volume129
Issue number5
DOIs
StatePublished - 2016

Keywords

  • Apoptosis
  • Appoptosin
  • MFN1
  • MFN2
  • MITOL
  • Mitochondrial dynamics

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Zhang, C., Shi, Z., Zhang, L., Zhou, Z., Zheng, X., Liu, G., Bu, G., Fraser, P. E., Xu, H., & Zhang, Y. W. (2016). Appoptosin interacts with mitochondrial outer-membrane fusion proteins and regulates mitochondrial morphology. Journal of cell science, 129(5), 994-1002. https://doi.org/10.1242/jcs.176792