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OPA1‐dependent cristae modulation is essential for cellular adaptation to metabolic demand

2014; Springer Nature; Volume: 33; Issue: 22 Linguagem: Inglês

10.15252/embj.201488349

1460-2075

David A. Patten, Jacob Wong, Mireille Khacho, Vincent Soubannier, Ryan J. Mailloux, Karine Pilon‐Larose, Jason G. MacLaurin, David S. Park, Heidi M. McBride, Laura Trinkle‐Mulcahy, Mary‐Ellen Harper, Marc Germain, Ruth S. Slack,

Genetics, Aging, and Longevity in Model Organisms

Abstract Cristae, the organized invaginations of the mitochondrial inner membrane, respond structurally to the energetic demands of the cell. The mechanism by which these dynamic changes are regulated and the consequences thereof are largely unknown. Optic atrophy 1 ( OPA 1) is the mitochondrial GTP ase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA 1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA 1's role in mitochondrial fusion, since an OPA 1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA 1 was required for resistance to starvation‐induced cell death, for mitochondrial respiration, for growth in galactose media and for maintenance of ATP synthase assembly, independently of its fusion activity. We identified mitochondrial solute carriers ( SLC 25A) as OPA 1 interactors and show that their pharmacological and genetic blockade inhibited OPA 1 oligomerization and function. Thus, we propose a novel way in which OPA 1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC 25A protein‐dependent manner.