Role of the mitochondria in the formation of a protein complex required for theactivation of cholesterol transport and steroid synthesis

PODESTA E. J

Texas

Simposio; Conference on the Adrenal Cortex. Satelite Symposium of the Endocrine Society USA.; 2012

National Institute of Health

ROLE OF THE MITOCHONDRIA IN THE FORMATION OF A PROTEIN COMPLEX REQUIRED FOR THE ACTIVATION OF CHOLESTEROL TRANSPORT AND STEROIDS SYNTHESIS?.Ernesto J Podestá. INBIOMED. School of Medicine. University of Buenos Aires. Argentina. 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 dynamics (a balance in fusion/fission events) might be relevant for this process. In the present study, we showed that the hormonal stimulation triggers mitochondrial fusion into tubular-shaped structures and that mitochondrial fusion does not only correlate-with but also is an essential step of steroid production, being both events dependent 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 modulate mitochondrial fusion and ERK1/2 localization in the mitochondrion. Strikingly, we found that mitofusin 2 (Mfn2) expressions, 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 dynamics 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.