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Open Access

Membrane depolarization activates the mitochondrial protease OMA1 by stimulating self‐cleavage

Kuan Zhang, Huihui Li, Zhiyin Song

Author Affiliations

  1. Kuan Zhang1,
  2. Huihui Li1 and
  3. Zhiyin Song*,1
  1. 1College of Life Sciences, Wuhan University, Wuhan, China
  1. *Corresponding author. Tel: +86 27 68752235; Fax: +86 551 63606264; E‐mail: songzy{at}whu.edu.cn

Abstract

Mitochondrial inner membrane fusion depends on the dynamin‐related GTPase OPA1 and the function of OPA1 is regulated by proteolytic cleavage. The mitochondrial proteases Yme1L and OMA1 cleave OPA1 at S2 and S1 sites, respectively. Here, we show that OMA1 is cleaved to a short form (S‐OMA1) by itself upon mitochondrial membrane depolarization; S‐OMA1 is degraded quickly but could be stabilized by CCCP treatment or Prohibitin knockdown in cells. In addition, OMA1 processing is positively correlated with OPA1 cleavage at the S1 site and the regulation of mitochondrial morphology. Thus, our results reveal the molecular mechanism for OMA1 activation toward OPA1 processing.

Synopsis

Embedded Image

The dynamin‐related GTPase OPA1 regulates mitochondrial inner membrane fusion and is activated by Yme1L‐ and OMA1‐mediated proteolytic cleavage. This study reveals that OMA1 undergoes self‐cleavage upon mitochondrial membrane depolarization under cellular stress conditions. The processing of OMA1 is positively correlated with its activity toward OPA1 cleavage.

  • OMA1, the protease that processes OPA1, undergoes self‐cleavage upon mitochondrial membrane depolarization

  • The processing of OMA1 is positively correlated with its activity toward OPA1 cleavage.

  • Received November 18, 2013.
  • Revision received March 5, 2014.
  • Accepted March 6, 2014.

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