Protease OMA1 modulates mitochondrial bioenergetics and ultrastructure through dynamic association with MICOS complex.
Protease OMA1 modulates mitochondrial bioenergetics and ultrastructure through dynamic association with MICOS complex.
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DOI：
10.1016/j.isci.2021.102119
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发表时间：
2021-02-19
期刊：
影响因子：
5.8
通讯作者：
Khalimonchuk O
中科院分区：
文献类型：
--
作者：
Viana MP;Levytskyy RM;Anand R;Reichert AS;Khalimonchuk O
线粒体超微结构的重塑是细胞器生理学和细胞凋亡的关键过程。尽管线粒体接触部位和脊连接组织系统(MICOS)和视神经萎缩1(OPA1)在这一过程中的关键作用已经确定，但其调控机制仍不完全清楚。在这里，我们发现金属多肽酶OMA1除了在线粒体分裂中发挥作用外，还通过与MICOS的动态结合来维持膜间连通性。这种结合独立于OPA1，通过MICOS亚单位MIC60介导，对于MICOS和膜间接触的稳定性是重要的。OMA1-MICOS继电器是获得最佳生物能量输出和细胞凋亡所必需的。OMA1的丢失会影响这些活性；值得注意的是，可以通过模拟MICOS的膜间桥来缓解这种影响。因此，在基础和应激条件下，线粒体的结构和生物能量学需要依赖于OMA1的超微结构支持，这表明OMA1在线粒体生理学中的作用以前不为人所知。金属蛋白酶OMA1与MICOS复合体的物理联系OMA1-MICOS结合对膜间连接很重要膜桥接减轻OMA1−/−细胞的生物能量和凋亡缺陷以前未知的OMA1在线粒体生理学中的作用揭示分子生物学；细胞生物学；细胞生物学的组织方面
Remodeling of mitochondrial ultrastructure is a process that is critical for organelle physiology and apoptosis. Although the key players in this process—mitochondrial contact site and cristae junction organizing system (MICOS) and Optic Atrophy 1 (OPA1)—have been characterized, the mechanisms behind its regulation remain incompletely defined. Here, we found that in addition to its role in mitochondrial division, metallopeptidase OMA1 is required for the maintenance of intermembrane connectivity through dynamic association with MICOS. This association is independent of OPA1, mediated via the MICOS subunit MIC60, and is important for stability of MICOS and the intermembrane contacts. The OMA1-MICOS relay is required for optimal bioenergetic output and apoptosis. Loss of OMA1 affects these activities; remarkably it can be alleviated by MICOS-emulating intermembrane bridge. Thus, OMA1-dependent ultrastructure support is required for mitochondrial architecture and bioenergetics under basal and stress conditions, suggesting a previously unrecognized role for OMA1 in mitochondrial physiology. Metalloprotease OMA1 is physically associated with MICOS complex OMA1-MICOS association is important for intermembrane connectivity Membrane bridging alleviates bioenergetic and apoptotic defects in oma1−/− cells Previously unrecognized role of OMA1 in mitochondrial physiology is revealed Molecular Biology; Cell Biology; Organizational Aspects of Cell Biology
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影响因子：
11.1
作者：
Genin EC;Plutino M;Bannwarth S;Villa E;Cisneros-Barroso E;Roy M;Ortega-Vila B;Fragaki K;Lespinasse F;Pinero-Martos E;Augé G;Moore D;Burté F;Lacas-Gervais S;Kageyama Y;Itoh K;Yu-Wai-Man P;Sesaki H;Ricci JE;Vives-Bauza C;Paquis-Flucklinger V
通讯作者：
Paquis-Flucklinger V
影响因子：
5.3
作者：
Desmurs, Marjorie;Foti, Michelangelo;Lane, Lydie
通讯作者：
Lane, Lydie
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
4.6
作者：
Bohovych I;Fernandez MR;Rahn JJ;Stackley KD;Bestman JE;Anandhan A;Franco R;Claypool SM;Lewis RE;Chan SS;Khalimonchuk O
通讯作者：
Khalimonchuk O
ChChd3 是一种线粒体内膜蛋白，对于维持嵴完整性和线粒体功能至关重要。
DOI：
10.1074/jbc.m110.171975
发表时间：
2011-01-28
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Darshi M;Mendiola VL;Mackey MR;Murphy AN;Koller A;Perkins GA;Ellisman MH;Taylor SS
通讯作者：
Taylor SS