• 作者： Karen G. Rosal, Wei-Yi Chen & Bon-chu Chung
• 作者服務機構： 1.Graduate Institute of Biomedical Sciences, Neuroscience and Brain Disease Center, China Medical University, Taichung, 404, Taiwan 2.Institute of Biochemistry and Molecular Biology, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan 3.Institute of Molecular Biology, Academia Sinica, Taipei, 115, Taiwan 4.Molecular Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center, Taipei, 115, Taiwan
• 中文摘要：
• 英文摘要：
  Background
  CYP11A1 is a protein located in the inner membrane of mitochondria catalyzing the first step of steroid synthesis. As a marker gene for steroid-producing cells, the abundance of CYP11A1 characterizes the extent of steroidogenic cell differentiation. Besides, the mitochondria of fully differentiated steroidogenic cells are specialized with tubulovesicular cristae. The participation of CYP11A1 in the change of mitochondrial structure and the differentiation of steroid-producing cells, however, has not been investigated.
  
  Methods
  We engineered nonsteroidogenic monkey kidney COS1 cells to express CYP11A1 upon doxycycline induction and examined the mitochondrial structure of these cells. We also mapped the CYP11A1 domains that confer structural changes of mitochondria. We searched for CYP11A1-interacting proteins and investigated the role of this interacting protein in shaping mitochondrial structure. Finally, we examined the effect of CYP11A1 overexpression on the amount of mitochondrial contact site and cristae organizing system.
  
  Results
  We found that CYP11A1 overexpression led to the formation of tubulovesicular cristae in mitochondria. We also identified the A’-helix located at amino acid #57–68 to be sufficient for membrane insertion and crista remodeling. We identified heat shock protein 60 (Hsp60) as the CYP11A1-interacting protein and showed that Hsp60 is required for CYP11A1 accumulation and crista remodeling. Finally, we found that the small MIC10 subcomplex of the mitochondrial contact site and cristae organizing system was reduced when CYP11A1 was overexpressed.
  
  Conclusions
  CYP11A1 participates in the formation of tubulovesicular cristae in the mitochondria of steroidogenic cells. Its A’-helix is sufficient for the formation of tubulovesicular cristae and for protein integration into the membrane. CYP11A1 interacts with Hsp60, which is required for CYP11A1 accumulation. The accumulation of CYP11A1 leads to the reduction of MIC10 complex and changes mitochondrial structure.
• 中文關鍵字：
• 英文關鍵字： Steroidogenesis, Pregnenolone, P450scc, Hsp60, Membrane, MIC10, Mitochondrial structure, Cristae remodeling