SLP-2 is required for stress-induced mitochondrial hyperfusion.
Mitochondria are dynamic organelles, the morphology of which results from an equilibrium between two opposing processes, fusion and fission. Mitochondrial fusion relies on dynamin-related GTPases, the mitofusins (MFN1 and 2) in the outer mitochondrial membrane and OPA1 (optic atrophy 1) in the inner mitochondrial membrane. Apart from a role in the maintenance of mitochondrial DNA, little is known about the physiological role of mitochondrial fusion. Here we report that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses. This process precedes mitochondrial fission when it is triggered by apoptotic stimuli such as UV irradiation or actinomycin D. Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2. In the absence of SLP-2, L-OPA1 is lost and SIMH is prevented. SIMH is accompanied by increased mitochondrial ATP production and represents a novel adaptive pro-survival response against stress.
Tondera
Daniel
D
Department of Cell Biology, University of Geneva, Geneva, Switzerland.
Grandemange
Stéphanie
S
Jourdain
Alexis
A
Karbowski
Mariusz
M
Mattenberger
Yves
Y
Herzig
Sébastien
S
Da Cruz
Sandrine
S
Clerc
Pascaline
P
Raschke
Ines
I
Merkwirth
Carsten
C
Ehses
Sarah
S
Krause
Frank
F
Chan
David C
DC
Alexander
Christiane
C
Bauer
Christoph
C
Youle
Richard
R
Langer
Thomas
T
Martinou
Jean-Claude
JC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003609:Dactinomycin / Q000633:toxicity; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D020558:GTP Phosphohydrolases / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects; D013312:Stress, Physiological; D014466:Ultraviolet Rays
D008565:Membrane Proteins; C424134:Sytl2 protein, mouse; D003609:Dactinomycin; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C488750:Mfn1 protein, mouse; C498809:Opa1 protein, mouse