OPA1, a large GTPase of the dynamin superfamily, mediates fusion of the mitochondrial inner membranes, regulates cristae morphology, and maintains respiratory chain function. Inner-membrane-anchored long forms of OPA1 (l-OPA1) are proteolytically processed by the OMA1 or YME1L proteases, acting at cleavage sites S1 and S2 respectively, to produce short forms (s-OPA1). In both mouse and human, half of the mRNA splice forms of Opa1 are constitutively processed to yield exclusively s-OPA1. However, the function of s-OPA1 in mitochondrial fusion has been debated, because in some stress conditions, s-OPA1 is dispensable for fusion. By constructing cells in which the Opa1 locus no longer produces transcripts with S2 cleavage sites, we generated a simplified system to identify the new YME1L-dependent site S3 that mediates constitutive and complete cleavage of OPA1. We show that mitochondrial morphology is highly sensitive to the ratio of l-OPA1 to s-OPA1, indicating that s-OPA1 regulates mitochondrial fusion.

OPA1，大GTP酶的发动蛋白超家族，线粒体内膜的介导融合，调节嵴形态，并维持呼吸链功能。内-膜-锚定的长OPA1（1- OPA1）的形式蛋白水解由OMA1或YME1L蛋白酶进行处理，分别在切割位点S1和S2作用，以产生短形式（S-OPA1）。在小鼠和人的mRNA的剪接形式半OPA1被组成处理以产生专门S-OPA1。然而，在线粒体融合S-OPA1的功能一直争论不休，因为在一些应激条件，S-OPA1是可有可无的融合。通过构建细胞，其中OPA1轨迹不再产生成绩单与S2切割位点，我们产生了一个简化的系统，以确定新的YME1L相关网站S3是介导组成和OPA1的完全解理。我们表明，线粒体形态是1- OPA1为s OPA1的比例高度敏感的，这表明S-OPA1调节线粒体融合。