Steroidogenic Enzyme CYP11A1 Remodels Mitochondrial Cristae

Program: Abstracts - Orals, Poster Previews, and Posters
Session: SUN 203-235-Steroid Hormone Actions, Biosynthesis and Metabolism (posters)
Bench to Bedside
Sunday, April 3, 2016: 1:15 PM-3:15 PM
Exhibit/Poster Hall (BCEC)

Poster Board SUN 213
Bonchu Chung*1 and Yu Chien2
1Academia Sinica, Taipei, Taiwan, 2Academia Sinica, Nankang, Taipei, Taiwan
Mitochondria are characterized by lamellar cristae that support the assembly of respiratory supercomplex for ATP production. These cristae also assume other shapes in some cells. The significance of this shape change and the control of cristae morphology are still unclear. Here, we found that mitochondrial cristae became tubular-vesicular accompanied by increased expression of steroidogenic enzyme CYP11A1 during differentiation of luteal and adrenocortical cells. Overexpression of CYP11A1 in non-steroidogenic COS-1 and HeLa cells remodeled cristae from lamellar to tubular-vesicular as examined by electron microscopy. In contrast, depletion of CYP11A1 in mouse ovarian corpus luteum led to degeneration of mitochondrial cristae. CYP11A1 resides in the inner mitochondrial membrane to catalyze steroid synthesis using electrons transported through the membrane. Inactive form (V415E) of CYP11A1 still induced the formation of tubular-vesicular cristae. We found that the first 85 amino acids of CYP11A1 containing the N-terminal putative membrane-anchoring A’ helix were sufficient to change cristae structure. This domain also disrupted the integrity of mitochondrial contact site and cristae organizing system (MICOS) complex. Therefore, we conclude that CYP11A1 in the mitochondrial membrane disrupts MICOS complex and remodels lamellar mitochondrial cristae into the vesicular type, therefore diverts electrons from respiration toward steroidogenesis during steroidogenic cell differentiation.

Nothing to Disclose: BC, YC

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