This study investigates the relationship between mitochondrial ultrastructure and respiratory function, focusing on the role of cristae shape in the assembly and stability of respiratory chain supercomplexes (RCS). The authors demonstrate that genetic and apoptotic manipulations of cristae structure affect the assembly and activity of RCS both in vitro and in vivo, independent of changes in mitochondrial protein synthesis or outer mitochondrial membrane permeabilization. They show that the efficiency of mitochondria-dependent cell growth depends on cristae shape, suggesting that RCS assembly is linked to membrane morphology and function. The study also explores the role of OPA1, a key regulator of cristae morphology, in RCS assembly and respiratory function, finding that conditional ablation of OPA1 impairs cristae shape, RCS assembly, and respiratory function. Overexpression of OPA1 increases RCS assembly and respiratory function, further supporting the link between cristae shape and RCS organization. The findings highlight the importance of cristae shape in maintaining mitochondrial respiratory efficiency and cell growth.This study investigates the relationship between mitochondrial ultrastructure and respiratory function, focusing on the role of cristae shape in the assembly and stability of respiratory chain supercomplexes (RCS). The authors demonstrate that genetic and apoptotic manipulations of cristae structure affect the assembly and activity of RCS both in vitro and in vivo, independent of changes in mitochondrial protein synthesis or outer mitochondrial membrane permeabilization. They show that the efficiency of mitochondria-dependent cell growth depends on cristae shape, suggesting that RCS assembly is linked to membrane morphology and function. The study also explores the role of OPA1, a key regulator of cristae morphology, in RCS assembly and respiratory function, finding that conditional ablation of OPA1 impairs cristae shape, RCS assembly, and respiratory function. Overexpression of OPA1 increases RCS assembly and respiratory function, further supporting the link between cristae shape and RCS organization. The findings highlight the importance of cristae shape in maintaining mitochondrial respiratory efficiency and cell growth.