Mitochondrial OMA1 and OPA1 as Gatekeepers of Organellar Structure/Function and Cellular Stress Response.
Mitochondrial OMA1 and OPA1 as Gatekeepers of Organellar Structure/Function and Cellular Stress Response.
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DOI：
10.3389/fcell.2021.626117
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发表时间：
2021
影响因子：
5.5
通讯作者：
St Vallier S
中科院分区：
文献类型：
--
作者：
Gilkerson R;De La Torre P;St Vallier S
哺乳动物线粒体正在成为细胞生命/死亡和发育结果的关键应激反应贡献者。作为分布在整个细胞中的细胞器网络，线粒体通过高度敏感的结构动力学对细胞刺激和应激做出反应，特别是在能量要求高的细胞环境中，如心脏和肌肉组织。融合允许单个线粒体形成相互连接的网状网络，而分裂将网络分成囊泡细胞器的集合。至关重要的是，视神经萎缩-1（optic atrophy-1，OPA 1）直接将线粒体结构和生物能量功能联系起来：当跨内膜的跨膜电位（Δ μ m）完整时，长的L-OPA 1亚型进行线粒体内膜的融合。当Δ Δ Δ Δ m丢失时，L-OPA 1被应激敏感性OMA 1金属蛋白酶切割成短的、融合失活的S-OPA 1亚型，导致线粒体网络崩溃成碎片化的细胞器群体。这种蛋白水解机制提供了细胞器结构/功能的灵敏调节，但也直接与凋亡因子结合，作为线粒体参与细胞应激反应的主要机制。此外，新出现的证据表明，这种蛋白水解机制可能对细胞发育程序至关重要，特别是在心脏，神经元和干细胞环境中。OMA 1作为一个关键的线粒体应激敏感蛋白酶的作用激发了令人兴奋的新问题，其机制的调节和相互作用，以及其更广泛的重要性，通过参与细胞凋亡，应激反应和发育途径。
Mammalian mitochondria are emerging as a critical stress-responsive contributor to cellular life/death and developmental outcomes. Maintained as an organellar network distributed throughout the cell, mitochondria respond to cellular stimuli and stresses through highly sensitive structural dynamics, particularly in energetically demanding cell settings such as cardiac and muscle tissues. Fusion allows individual mitochondria to form an interconnected reticular network, while fission divides the network into a collection of vesicular organelles. Crucially, optic atrophy-1 (OPA1) directly links mitochondrial structure and bioenergetic function: when the transmembrane potential across the inner membrane (ΔΨm) is intact, long L-OPA1 isoforms carry out fusion of the mitochondrial inner membrane. When ΔΨm is lost, L-OPA1 is cleaved to short, fusion-inactive S-OPA1 isoforms by the stress-sensitive OMA1 metalloprotease, causing the mitochondrial network to collapse to a fragmented population of organelles. This proteolytic mechanism provides sensitive regulation of organellar structure/function but also engages directly with apoptotic factors as a major mechanism of mitochondrial participation in cellular stress response. Furthermore, emerging evidence suggests that this proteolytic mechanism may have critical importance for cell developmental programs, particularly in cardiac, neuronal, and stem cell settings. OMA1’s role as a key mitochondrial stress-sensitive protease motivates exciting new questions regarding its mechanistic regulation and interactions, as well as its broader importance through involvement in apoptotic, stress response, and developmental pathways.
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影响因子：
17.1
作者：
Acin-Perez, Rebeca;Victoria Lechuga-Vieco, Ana;Antonio Enriquez, Jose
通讯作者：
Antonio Enriquez, Jose
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：
64.8
作者：
Faelber, Katja;Dietrich, Lea;Daumke, Oliver
通讯作者：
Daumke, Oliver
影响因子：
4.6
作者：
Daverey, Amita;Levytskyy, Roman M.;Kidambi, Srivatsan
通讯作者：
Kidambi, Srivatsan
影响因子：
2.7
作者：
Guillery, Olwenn;Malka, Florence;Rojo, Manuel
通讯作者：
Rojo, Manuel