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EMBO J. 2014 Nov 18;33(22):2676-91. doi: 10.15252/embj.201488349. Epub 2014 Oct 8.

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

Author information

1
Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
2
Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
3
Department of Biochemistry, Microbiology & Immunology, University of Ottawa, Ottawa, ON, Canada.
4
Département de Biologie Médicale, Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada rslack@uottawa.ca marc.germain1@uqtr.ca.
5
Department of Cellular & Molecular Medicine, University of Ottawa, Ottawa, ON, Canada rslack@uottawa.ca marc.germain1@uqtr.ca.

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 (OPA1) is the mitochondrial GTPase responsible for inner membrane fusion and maintenance of cristae structure. Here, we report that OPA1 responds dynamically to changes in energetic conditions to regulate cristae structure. This cristae regulation is independent of OPA1's role in mitochondrial fusion, since an OPA1 mutant that can still oligomerize but has no fusion activity was able to maintain cristae structure. Importantly, OPA1 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 (SLC25A) as OPA1 interactors and show that their pharmacological and genetic blockade inhibited OPA1 oligomerization and function. Thus, we propose a novel way in which OPA1 senses energy substrate availability, which modulates its function in the regulation of mitochondrial architecture in a SLC25A protein-dependent manner.

KEYWORDS:

ATP synthase; OPA1; SLC25A; cristae; mitochondria

PMID:
25298396
PMCID:
PMC4282575
DOI:
10.15252/embj.201488349
[Indexed for MEDLINE]
Free PMC Article

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