The MICOS complex (mitochondrial contact site and cristae organizing system) is essential for mitochondrial inner membrane organization and mitochondrial membrane contacts,however,the molecular regulation of MICOS assembly and the physiological functions of MICOS in mammals remain obscure.Here,we report that Mic60/Mitofilin plays critical role for the MICOS assembly which determine the mitochondrial morphology and mtDNA organization.The loss of Mic60/Mitofilin or Mic 19/CHCHD3 results in instability of other MICOS components,disassembly of MICOS complex and disorganized mitochondrial cristae.We show that there exists direct interaction between Mic60/Mitofilin and Mic19/CHCHD3 which is crucial for their stabilization in mammals.