Hormone-dependent mitochondrial fusion regulates the translocation

PODEROSO C, DUARTE A, COOKE M, ORLANDO U, CORNEJO MACIEL F, SORIA G, GOTTIFREDI V, PODESTA EJ.

Congreso; XLVII Reunión Anual de Investigación en Bioquímica y Biología Molecular (SAIB); 2011

Mitochondrial dynamics (fusion-fission) is important for maintaining the integrity of these organelles and many cellular processes. The activation of the cAMP signal leads to a translocation of PKA and ERK to the mitochondria to form a multiprotein complex necessary for cholesterol transport. However, neither PKA nor ERK present mitochondrial targeting signal. The aim of this study is to evaluate if hormonal stimulation could promote mitochondrial morphology changes that might regulate specialized cellular functions. We transfected MA-IO Leydig cells with a specific mitochondrial marker, mtYFP and visualized the samples by confocal microscopy. Hormonal stimulation, with hCG or 8Br-cAMP(permeable analogue of cAMP) promotes a clear rearrangement of the mitochondrial network, from a cluster type in control cells to a fusion-like tubular shape. Treatment of the cells with CCCP, a proton ionophore, demonstrates that the mitochondrial membrane potential is required for this reorganization. Also, mitochondrial rearrangement produces the association of the acyl-CoA synthetase 4 with the organelle. The protein tyrosine phosphatase SHP2 knockdown abolishes the morphological changes and translocation of ERK. Thus, it seems that SHP2 may control mitochondrial dynamics allowing the recruitment of crucial mitochondrial proteins to generate a multiprotein complex that regulates cellular functions.