Chronic Expression of RCAN1-1L Protein Induces Mitochondrial Autophagy and Metabolic Shift from Oxidative Phosphorylation to Glycolysis in Neuronal Cells
Chronic Expression of RCAN1-1L Protein Induces Mitochondrial Autophagy and Metabolic Shift from Oxidative Phosphorylation to Glycolysis in Neuronal Cells
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DOI：
10.1074/jbc.m111.305342
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发表时间：
2012-04-20
影响因子：
4.8
通讯作者：
Davies, Kelvin J. A.
中科院分区：
文献类型：
--
作者：
Ermak, Gennady;Sojitra, Sonal;Davies, Kelvin J. A.
RCAN1基因的表达可被多种胁迫诱导。RCAN1蛋白(RCAN1)既有保护作用，也有有害作用，与常见的人类病理有关。然而，RCAN1的作用机制仍然知之甚少。我们发现RCAN1是线粒体自噬(有丝分裂)的调节者，并证明RCAN1-1L的诱导可以导致线粒体的戏剧性降解。这种降解的机制涉及腺核苷酸转运体和线粒体通透性转换孔的打开。我们还证明了RCAN1-1L的诱导可以将细胞的生物能量学从有氧呼吸转变为糖酵解，但RCAN1-1L对细胞分裂的影响很小，而对细胞存活有累积的负面影响。这些结果揭示了RCAN1可以保护或损害细胞的机制，以及它们可能在人类病理中发挥作用的机制。他们还表明，RCAN1在自噬和线粒体通透性转换孔等难以捉摸的现象中发挥着重要作用。
Expression of the RCAN1 gene can be induced by multiple stresses. RCAN1 proteins (RCAN1s) have both protective and harmful effects and are implicated in common human pathologies. The mechanisms by which RCAN1s function, however, remain poorly understood. We identify RCAN1s as regulators of mitochondrial autophagy (mitophagy) and demonstrate that induction of RCAN1-1L can cause dramatic degradation of mitochondria. The mechanisms of such degradation involve the adenine nucleotide translocator and mitochondrial permeability transition pore opening. We also demonstrate that RCAN1-1L induction can shift cellular bioenergetics from aerobic respiration to glycolysis, yet RCAN1-1L has very little effect on cell division, whereas it has a cumulative negative effect on cell survival. These results shed the light on mechanisms by which RCAN1s can protect or harm cells and by which they may operate in human pathologies. They also suggest that RCAN1s are important players in autophagy and such elusive phenomena as the mitochondrial permeability transition pore.