AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.
AMPK-dependent phosphorylation of MTFR1L regulates mitochondrial morphology.
复制标题
AMPK依赖的MTFR1L磷酸化调节线粒体形态。
DOI：
10.1126/sciadv.abo7956
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发表时间：
2022-11-11
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体是动态细胞器，在代谢改变时经历膜重塑事件，以产生足够的线粒体网络。在这里，我们研究了线粒体分裂调节因子1样蛋白(MTFR1L)的功能，这是一种在磷酸蛋白质组筛选中被鉴定为潜在的AMP激活蛋白激酶(AMPK)底物的未鉴定蛋白。我们发现MTFR1L是一种线粒体膜外定位蛋白，调节线粒体的形态。MTFR1L的丢失导致线粒体延长，与增加线粒体融合事件和线粒体融合蛋白水平相关，视神经萎缩1。从机制上，我们证明MTFR1L被AMPK磷酸化，从而控制MTFR1L在调节哺乳动物细胞系和活体小鼠皮质神经元中的线粒体形态方面的功能。此外，我们证明了MTFR1L是应激诱导的AMPK依赖的线粒体断裂所必需的。综上所述，这些发现确认MTFR1L是一种关键的线粒体蛋白，通过调节线粒体动力学来传递AMPK依赖的代谢变化。MTFR1L作为控制线粒体动力学的线粒体AMPK底物的功能特征
Mitochondria are dynamic organelles that undergo membrane remodeling events in response to metabolic alterations to generate an adequate mitochondrial network. Here, we investigated the function of mitochondrial fission regulator 1-like protein (MTFR1L), an uncharacterized protein that has been identified in phosphoproteomic screens as a potential AMP-activated protein kinase (AMPK) substrate. We showed that MTFR1L is an outer mitochondrial membrane–localized protein modulating mitochondrial morphology. Loss of MTFR1L led to mitochondrial elongation associated with increased mitochondrial fusion events and levels of the mitochondrial fusion protein, optic atrophy 1. Mechanistically, we show that MTFR1L is phosphorylated by AMPK, which thereby controls the function of MTFR1L in regulating mitochondrial morphology both in mammalian cell lines and in murine cortical neurons in vivo. Furthermore, we demonstrate that MTFR1L is required for stress-induced AMPK-dependent mitochondrial fragmentation. Together, these findings identify MTFR1L as a critical mitochondrial protein transducing AMPK-dependent metabolic changes through regulation of mitochondrial dynamics. Functional characterization of MTFR1L as a mitochondrial AMPK substrate controlling mitochondrial dynamics.
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影响因子：
11.1
作者：
Janer A;Prudent J;Paupe V;Fahiminiya S;Majewski J;Sgarioto N;Des Rosiers C;Forest A;Lin ZY;Gingras AC;Mitchell G;McBride HM;Shoubridge EA
通讯作者：
Shoubridge EA
影响因子：
21.3
作者：
通讯作者：
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Neurogenin2调节在callosum中间投射的皮质锥体神经元的初始轴突引导。
影响因子：
3.6
作者：
Hand R;Polleux F
通讯作者：
Polleux F
DOI：
10.1073/pnas.2025932118
发表时间：
2021-09-14
影响因子：
11.1
作者：
Drake JC;Wilson RJ;Laker RC;Guan Y;Spaulding HR;Nichenko AS;Shen W;Shang H;Dorn MV;Huang K;Zhang M;Bandara AB;Brisendine MH;Kashatus JA;Sharma PR;Young A;Gautam J;Cao R;Wallrabe H;Chang PA;Wong M;Desjardins EM;Hawley SA;Christ GJ;Kashatus DF;Miller CL;Wolf MJ;Periasamy A;Steinberg GR;Hardie DG;Yan Z
通讯作者：
Yan Z
影响因子：
29
作者：
Civiletto G;Varanita T;Cerutti R;Gorletta T;Barbaro S;Marchet S;Lamperti C;Viscomi C;Scorrano L;Zeviani M
通讯作者：
Zeviani M