Transmembrane segments of the dynamin Msp1p uncouple its functions in the control of mitochondrial morphology and genome maintenance.
Mitochondrial morphology depends on the equilibrium between antagonistic fission and fusion forces acting on mitochondrial membranes. Inactivation of fusion induces the loss of mtDNA. When both fusion and fission are simultaneously inactivated, the loss of mtDNA is alleviated, along with mitochondrial fragmentation. Mechanisms involved in mtDNA maintenance thus seem to depend on a coordinated regulation of fusion and fission forces. We have studied the role of the dynamin Msp1p, a fusion effector in mitochondrial morphology, in relation to the maintenance of mtDNA. Two hydrophobic regions of Msp1p, predicted to be transmembrane segments, were shown to anchor the long form of the protein into mitochondrial membranes, whereas the short form, lacking these two domains, behaved as a peripheral membrane protein. Both domains were essential for the fusogenic activity of Msp1p, but deletion of the second domain alone induced loss of mtDNA and thus lethality. Our results demonstrate that the role of Msp1p in the control of mitochondrial morphology is distinct from that required for genome maintenance, and that only the latter function is essential for cell viability. This parallels recent observations that have distinguished the role of OPA1, the human orthologue of Msp1p, in mitochondrial dynamics from that in cristae organization and apoptosis. Furthermore, our observations may contribute to our understanding of the pathological mechanisms resulting from mutations in OPA1 that give rise to the ADOA syndromes.
Diot
Alan
A
Université de Toulouse, UPS and CNRS UMR 5241, Laboratoire Métabolisme Plasticité Mitochondries, F-31000, France.
Guillou
Emmanuelle
E
Daloyau
Marlène
M
Arnauné-Pelloquin
Laetitia
L
Emorine
Laurent J
LJ
Belenguer
Pascale
P
D004272:DNA, Mitochondrial / Q000235:genetics*; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D005804:Genes, Lethal; D016681:Genome, Fungal; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D020033:Protein Isoforms; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
D004272:DNA, Mitochondrial; D020033:Protein Isoforms; D029702:Schizosaccharomyces pombe Proteins; C498345:Dnm1 protein, S pombe; D034281:Dynamins; C498344:Msp1 protein, S pombe