Regulation of mitochondria distribution by RhoA and formins.
The distribution of mitochondria is strictly controlled by the cell because of their vital role in energy supply, regulation of cytosolic Ca2+ concentration and apoptosis. We employed cultured mammalian CV-1 cells and Drosophila BG2-C2 neuronal cells with enhanced green fluorescent protein (EGFP)-tagged mitochondria to investigate the regulation of their movement and anchorage. We show here that lysophosphatidic acid (LPA) inhibits fast mitochondrial movements in CV-1 cells acting through the small GTPase RhoA. The action of RhoA is mediated by its downstream effectors: formin-homology family members mDia1 in mammalian cells and diaphanous in Drosophila. Overexpression of constitutively active mutant forms of formins leads to dramatic loss of mitochondrial motility and to their anchorage to actin microfilaments. Conversely, depletion of endogenous diaphanous protein in BG2-C2 cells by RNA interference (RNAi) stimulates the mitochondrial movement. These effects are not simply explained by increased cytoplasm viscosity resulting from an increased F-actin concentration since stimulators of Arp2/3-dependent actin polymerization and jasplakinolide do not cause inhibition. The observed effects are highly specific to mitochondria since perturbations of diaphanous or mDia1 have no effect on movement of other membrane organelles. Thus, mitochondrial movement is controlled by the small GTPase RhoA and this control is mediated by formins.
Minin
Alexander A
AA
Institute of Protein Research, Russian Academy of Sciences, Moscow 119988, Russia. minin@eimb.ru
Kulik
Alexander V
AV
Gyoeva
Fatima K
FK
Li
Ying
Y
Goshima
Gohta
G
Gelfand
Vladimir I
VI
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D004330:Drosophila; D000080865:Formins; D000882:Haplorhini; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D008840:Microfilament Proteins; D020742:rhoA GTP-Binding Protein; D002118:Calcium