Mitochondrial OPA1 cleavage is reversibly activated by differentiation of H9c2 cardiomyoblasts.
Mitochondrial OPA1 cleavage is reversibly activated by differentiation of H9c2 cardiomyoblasts.
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线粒体OPA1裂解通过H9c2成心肌细胞的分化被可逆地激活。
DOI：
10.1016/j.mito.2020.12.007
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发表时间：
2021-03
期刊：
影响因子：
4.4
通讯作者：
Gilkerson R
中科院分区：
文献类型：
--
作者：
Garcia I;Calderon F;la Torre P;Vallier SS;Rodriguez C;Agarwala D;Keniry M;Innis-Whitehouse W;Gilkerson R
视神经萎缩-1（Optic atrophy-1，OPA 1）是一种定位于线粒体内膜的动力蛋白样GTP酶，在内膜融合和嵴维持中起关键作用。OPA 1受线粒体跨膜电位（Δ μ m）调节：当Δ μ m完整时，长OPA 1亚型（L-OPA 1）进行内膜融合。在Δ m丧失后，L-OPA 1亚型被应激诱导型OMA 1金属蛋白酶蛋白水解切割成短（S-OPA 1）亚型，导致线粒体网络崩溃并促进细胞凋亡。在这里，我们表明，H9 c2成心肌细胞的L-OPA 1亚型在Δ m丢失的情况下保留，尽管存在OMA 1。然而，当H9 c2通过在低血清培养基中用视黄酸（RA）处理而分化为更心脏样表型时，Δ m的损失诱导L-OPA 1的稳健且可逆的切割和随后的OMA 1降解。这些发现表明，一个有效的发育开关调节Δ Δ Tm敏感的OPA 1切割，提示OPA 1稳态的新的发育和调节机制。
Optic atrophy-1 (OPA1) is a dynamin-like GTPase localized to the mitochondrial inner membrane, playing key roles in inner membrane fusion and cristae maintenance. OPA1 is regulated by the mitochondrial transmembrane potential (Δψm): when Δψm is intact, long OPA1 isoforms (L-OPA1) carry out inner membrane fusion. Upon loss of Δψm, L-OPA1 isoforms are proteolytically cleaved to short (S-OPA1) isoforms by the stress-inducible OMA1 metalloprotease, causing collapse of the mitochondrial network and promoting apoptosis. Here, we show that L-OPA1 isoforms of H9c2 cardiomyoblasts are retained under loss of Δψm, despite the presence of OMA1. However, when H9c2s are differentiated to a more cardiac-like phenotype via treatment with retinoic acid (RA) in low serum media, loss of Δψm induces robust, and reversible, cleavage of L-OPA1 and subsequent OMA1 degradation. These findings indicate that a potent developmental switch regulates Δψm-sensitive OPA1 cleavage, suggesting novel developmental and regulatory mechanisms for OPA1 homeostasis.
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