Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
Department of Physiology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia 30912.
J Biol Chem. 2014 Apr 25;289(17):11862-11872. doi: 10.1074/jbc.M113.533299. Epub 2014 Mar 13.
Dynamin-related membrane remodeling proteins regulate mitochondrial morphology by mediating fission and fusion. Although mitochondrial morphology is considered an important factor in maintaining mitochondrial function, a direct mechanistic link between mitochondrial morphology and function has not been defined. We report here a previously unrecognized cellular process of transient contraction of the mitochondrial matrix. Importantly, we found that this transient morphological contraction of mitochondria is accompanied by a reversible loss or decrease of inner membrane potential. Fission deficiency greatly amplified this phenomenon, which functionally exhibited an increase of inner membrane proton leak. We found that electron transport activity is necessary for the morphological contraction of mitochondria. Furthermore, we discovered that silencing the inner membrane-associated dynamin optic atrophy 1 (OPA1) in fission deficiency prevented mitochondrial depolarization and decreased proton leak without blocking mitochondrial contraction, indicating that OPA1 is a factor in coupling matrix contraction to mitochondrial depolarization. Our findings show that transient matrix contraction is a novel cellular mechanism regulating mitochondrial activity through the function of the inner membrane dynamin OPA1.
动力相关膜重塑蛋白通过介导分裂和融合来调节线粒体形态。尽管线粒体形态被认为是维持线粒体功能的一个重要因素，但线粒体形态和功能之间的直接机制联系尚未确定。我们在这里报告一个以前未被认识的细胞过程，即线粒体基质的短暂收缩。重要的是，我们发现线粒体的这种短暂形态收缩伴随着内膜电位的可逆丧失或下降。分裂缺陷大大放大了这一现象，其功能表现为内膜质子漏增加。我们发现电子传递活性对于线粒体的形态收缩是必需的。此外，我们发现，在分裂缺陷中沉默与内膜相关的视神经萎缩蛋白 1（OPA1）可防止线粒体去极化和质子漏减少，而不阻断线粒体收缩，表明 OPA1 是将基质收缩与线粒体去极化偶联的因素。我们的发现表明，短暂的基质收缩是一种通过内膜动力蛋白 OPA1 的功能调节线粒体活性的新的细胞机制。
