Mitochondrial Fusion Is Essential for Steroid Biosynthesis
Open Access
- 21 September 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (9), e45829
- https://doi.org/10.1371/journal.pone.0045829
Abstract
Although the contribution of mitochondrial dynamics (a balance in fusion/fission events and changes in mitochondria subcellular distribution) to key biological process has been reported, the contribution of changes in mitochondrial fusion to achieve efficient steroid production has never been explored. The mitochondria are central during steroid synthesis and different enzymes are localized between the mitochondria and the endoplasmic reticulum to produce the final steroid hormone, thus suggesting that mitochondrial fusion might be relevant for this process. In the present study, we showed that the hormonal stimulation triggers mitochondrial fusion into tubular-shaped structures and we demonstrated that mitochondrial fusion does not only correlate-with but also is an essential step of steroid production, being both events depend on PKA activity. We also demonstrated that the hormone-stimulated relocalization of ERK1/2 in the mitochondrion, a critical step during steroidogenesis, depends on mitochondrial fusion. Additionally, we showed that the SHP2 phosphatase, which is required for full steroidogenesis, simultaneously modulates mitochondrial fusion and ERK1/2 localization in the mitochondrion. Strikingly, we found that mitofusin 2 (Mfn2) expression, a central protein for mitochondrial fusion, is upregulated immediately after hormone stimulation. Moreover, Mfn2 knockdown is sufficient to impair steroid biosynthesis. Together, our findings unveil an essential role for mitochondrial fusion during steroidogenesis. These discoveries highlight the importance of organelles’ reorganization in specialized cells, prompting the exploration of the impact that organelle dynamics has on biological processes that include, but are not limited to, steroid synthesis.Keywords
This publication has 56 references indexed in Scilit:
- Mechanism of Neuroprotective Mitochondrial Remodeling by PKA/AKAP1PLoS Biology, 2011
- Tyrosine phosphatases as key regulators of StAR induction and cholesterol transport: SHP2 as a potential tyrosine phosphatase involved in steroid synthesisMolecular and Cellular Endocrinology, 2011
- Mitochondrial Fusion: Bax to the FussureDevelopmental Cell, 2011
- Mitochondria and the culture of the BorgBioEssays, 2010
- Mitochondrial fragmentation and superoxide anion production in coronary endothelial cells from a mouse model of type 1 diabetesDiabetologia, 2010
- Cholesterol transport in steroid biosynthesis: Role of protein–protein interactions and implications in disease statesBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2009
- A Mitochondrial Kinase Complex Is Essential to Mediate an ERK1/2-Dependent Phosphorylation of a Key Regulatory Protein in Steroid BiosynthesisPLOS ONE, 2008
- An arachidonic acid-preferring acyl-CoA synthetase is a hormone-dependent and obligatory protein in the signal transduction pathway of steroidogenic hormonesJournal of Molecular Endocrinology, 2005
- Interaction Theory of Mammalian MitochondriaBiochemical and Biophysical Research Communications, 2001
- Roles of microfilaments and intermediate filaments in adrenal steroidogenesisMicroscopy Research and Technique, 1997