Regulation of Mitochondrial Morphogenesis by Annexin A6

Marcin Chlystun, Michelangelo Campanella, Ah Lai Law, Michael R. Duchen, Lux Fatimathas, Tim P. Levine, Volker Gerke, Stephen E. Moss

Research output: Contribution to journalArticle

Abstract

Mitochondrial homeostasis is critical in meeting cellular energy demands, shaping calcium signals and determining susceptibility to apoptosis. Here we report a role for anxA6 in the regulation of mitochondrial morphogenesis, and show that in cells lacking anxA6 mitochondria are fragmented, respiration is impaired and mitochondrial membrane potential is reduced. In fibroblasts from AnxA6-/- mice, mitochondrial Ca2+ uptake is reduced and cytosolic Ca2+ transients are elevated. These observations led us to investigate possible interactions between anxA6 and proteins with roles in mitochondrial fusion and fission. We found that anxA6 associates with Drp1 and that mitochondrial fragmentation in AnxA6-/- fibroblasts was prevented by the Drp1 inhibitor mdivi-1. In normal cells elevation of intracellular Ca2+ disrupted the interaction between anxA6 and Drp1, displacing anxA6 to the plasma membrane and promoting mitochondrial fission. Our results suggest that anxA6 inhibits Drp1 activity, and that Ca2+-binding to anxA6 relieves this inhibition to permit Drp1-mediated mitochondrial fission.

Original languageEnglish
Article numbere53774
JournalPLoS One
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 18 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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