Mitochondria are quantifiably the most important sources of superoxide (O₂^●−) and hydrogen peroxide (H₂O₂) in mammalian cells. The overproduction of these molecules has been studied mostly in the contexts of the pathogenesis of human diseases and aging. However, controlled bursts in mitochondrial ROS production, most notably H₂O₂, also plays a vital role in the transmission of cellular information. Striking a balance between utilizing H₂O₂ in second messaging whilst avoiding its deleterious effects requires the use of sophisticated feedback control and H₂O₂ degrading mechanisms. Mitochondria are enriched with H₂O₂ degrading enzymes to desensitize redox signals. These organelles also use a series of negative feedback loops, such as proton leaks or protein S-glutathionylation, to inhibit H₂O₂ production. Understanding how mitochondria produce ROS is also important for comprehending how these organelles use H₂O₂ in eustress signaling. Indeed, twelve different enzymes associated with nutrient metabolism and oxidative phosphorylation (OXPHOS) can serve as important ROS sources. This includes several flavoproteins and respiratory complexes I-III. Progress in understanding how mitochondria generate H₂O₂ for signaling must also account for critical physiological factors that strongly influence ROS production, such as sex differences and genetic variances in genes encoding antioxidants and proteins involved in mitochondrial bioenergetics. In the present review, I provide an updated view on how mitochondria budget cellular H₂O₂ production. These discussions will focus on the potential addition of two acyl-CoA dehydrogenases to the list of ROS generators and the impact of important phenotypic and physiological factors such as tissue type, mouse strain, and sex on production by these individual sites.

中文翻译：

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线粒体活性氧生产的更新。

线粒体可量化为哺乳动物细胞中最重要的超氧化物（O ₂ ^{● -}）和过氧化氢（H ₂ O ₂）来源。这些分子的过量生产主要是在人类疾病和衰老的发病机制中进行的。但是，线粒体ROS产生的受控爆发（最明显的是H ₂ O _2）在细胞信息的传递中也起着至关重要的作用。为了在第二消息中利用H ₂ O ₂与避免其有害影响之间取得平衡，需要使用复杂的反馈控制和H ₂ O ₂降级机制。线粒体富含H ₂ O ₂降解酶以使氧化还原信号脱敏。这些细胞器还使用一系列负反馈回路，例如质子泄漏或蛋白质S-谷胱甘肽酰化，来抑制H ₂ O _2的产生。理解线粒体如何产生ROS对于理解这些细胞器如何在Estress信号转导中使用H ₂ O ₂也是重要的。实际上，与营养物代谢和氧化磷酸化（OXPHOS）相关的十二种不同的酶可以作为重要的ROS来源。这包括几种黄素蛋白和呼吸复合物I-III。线粒体如何产生H _2的进展用于信号传导的O ₂还必须说明严重影响ROS产生的关键生理因素，例如性别差异和编码抗氧化剂和线粒体生物能量学相关蛋白的基因的遗传变异。在当前的审查中，我提供有关线粒体如何预算细胞H ₂ O ₂生产的最新观点。这些讨论将集中于可能将两种酰基辅酶A脱氢酶添加到ROS生成器列表中，以及重要的表型和生理因素（如组织类型，小鼠品系和性别）对这些单个位点产生的影响。