Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency.
Respiratory chain complexes assemble into functional quaternary structures called supercomplexes (RCS) within the folds of the inner mitochondrial membrane, or cristae. Here, we investigate the relationship between respiratory function and mitochondrial ultrastructure and provide evidence that cristae shape determines the assembly and stability of RCS and hence mitochondrial respiratory efficiency. Genetic and apoptotic manipulations of cristae structure affect assembly and activity of RCS in vitro and in vivo, independently of changes to mitochondrial protein synthesis or apoptotic outer mitochondrial membrane permeabilization. We demonstrate that, accordingly, the efficiency of mitochondria-dependent cell growth depends on cristae shape. Thus, RCS assembly emerges as a link between membrane morphology and function.
Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy.
Sara
S
Cogliati
Christian
C
Frezza
Maria Eugenia
ME
Soriano
Tatiana
T
Varanita
Ruben
R
Quintana-Cabrera
Mauro
M
Corrado
Sara
S
Cipolat
Veronica
V
Costa
Alberto
A
Casarin
Ligia C
LC
Gomes
Ester
E
Perales-Clemente
Leonardo
L
Salviati
Patricio
P
Fernandez-Silva
Jose A
JA
Enriquez
Luca
L
Scorrano
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000737:chemistry / Q000378:metabolism; D019069:Cell Respiration; D004579:Electron Transport; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism; D016415:Sequence Alignment
D051023:BH3 Interacting Domain Death Agonist Protein; D046912:Multiprotein Complexes; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse