Title

Optic Atrophy 1- Dependent Mitochondrial Remodeling Controls Steroidogenesis in Trophoblasts

Document Type

Article

Publication Title

Current Biology

ISSN

0960-9822

Volume

22

Issue

13

First Page

1228

1234

Publication Date

2012

Abstract

During human pregnancy, placental trophoblasts differentiate and syncytialize into syncytiotrophoblasts that sustain progesterone production [1]. This process is accompanied by mitochondrial fragmentation and cristae remodeling [2], two facets of mitochondrial apoptosis, whose molecular mechanisms and functional consequences on steroidogenesis are unclear. Here we show that the mitochondria-shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis. During syncytialization of trophoblast BeWo cells, levels of the profission mitochondria-shaping protein Drp1 increase, and those of Opa1 and mitofusin (Mfn) decrease, leading to mitochondrial fragmentation and cristae remodeling. Manipulation of the levels of Opa1 reveal an inverse relationship with the efficiency of steroidogenesis in trophoblasts and in mouse embryonic fibroblasts where the mitochondrial steroidogenetic pathway has been engineered. In an in vitro assay, accumulation of cholesterol is facilitated in the inner membrane of isolated mitochondria lacking Opa1. Thus, Opa1-dependent inner membrane remodeling controls efficiency of steroidogenesis. (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Publication Information

Wasilewski, M., Rafelski, S. M., Robbins, J. R., Bakardjiev, A. I., & Scorrano, L (2012). Optic atrophy 1- dependent mitochondrial remodeling controls steroidogenesis in trophoblasts. Current Biology, 22(13), 1228-1234.

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