H2S remodels mitochondrial ultrastructure and destabilizes respiratory supercomplexes.

IF 4 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
David A Hanna, Brandon Chen, Yatrik M Shah, Oleh Khalimonchuk, Brian Cunniff, Ruma Banerjee
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引用次数: 0

Abstract

Mitochondrial form and function are intimately interconnected, responding to cellular stresses and changes in energy demand. Hydrogen sulfide, a product of amino acid metabolism, has dual roles as an electron transport chain substrate and complex IV (CIV) inhibitor, leading to a reductive shift, which has pleiotropic metabolic consequences. Luminal sulfide concentration in colon is high due to microbial activity, and in this study, we demonstrate that chronic sulfide exposure of colonocyte-derived cells leads to lower Mic60 and Mic19 expression that is correlated with a profound loss of cristae and lower mitochondrial networking. Sulfide-induced depolarization of the inner mitochondrial membrane activates Oma1-dependent cleavage of Opa1 and is associated with a profound loss of CI and CIV activities associated with respirasomes. Our study reveals a potential role for sulfide as an endogenous modulator of mitochondrial dynamics and suggests that this regulation is corrupted in hereditary or acquired diseases associated with elevated sulfide.

H2S重塑线粒体超微结构,破坏呼吸超复合体的稳定。
线粒体的形态和功能密切相关,对细胞压力和能量需求的变化作出反应。硫化氢是氨基酸代谢的产物,具有电子传递链底物和络合物IV (CIV)抑制剂的双重作用,导致还原性转移,具有多效性代谢后果。由于微生物活动,结肠内的腔内硫化物浓度很高,在本研究中,我们证明结肠细胞衍生细胞的慢性硫化物暴露导致Mic60和Mic19表达降低,这与嵴的严重缺失和线粒体网络的降低有关。硫化物诱导的线粒体内膜去极化激活了依赖于oma1的Opa1裂解,并与呼吸小体相关的CI和CIV活性的严重丧失有关。我们的研究揭示了硫化物作为线粒体动力学内源性调节剂的潜在作用,并表明这种调节在与硫化物升高相关的遗传性或获得性疾病中被破坏。
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来源期刊
Journal of Biological Chemistry
Journal of Biological Chemistry Biochemistry, Genetics and Molecular Biology-Biochemistry
自引率
4.20%
发文量
1233
期刊介绍: The Journal of Biological Chemistry welcomes high-quality science that seeks to elucidate the molecular and cellular basis of biological processes. Papers published in JBC can therefore fall under the umbrellas of not only biological chemistry, chemical biology, or biochemistry, but also allied disciplines such as biophysics, systems biology, RNA biology, immunology, microbiology, neurobiology, epigenetics, computational biology, ’omics, and many more. The outcome of our focus on papers that contribute novel and important mechanistic insights, rather than on a particular topic area, is that JBC is truly a melting pot for scientists across disciplines. In addition, JBC welcomes papers that describe methods that will help scientists push their biochemical inquiries forward and resources that will be of use to the research community.
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