The redox-active protein cytochrome c is a highly positively charged hemoglobin that regulates cell fate decisions of life and death. Under normal physiological conditions, cytochrome c is localized in the mitochondrial intermembrane space, and its distribution can extend to the cytosol, nucleus, and extracellular space under specific pathological or stress-induced conditions. In the mitochondria, cytochrome c acts as an electron carrier in the electron transport chain, facilitating adenosine triphosphate synthesis, regulating cardiolipin peroxidation, and influencing reactive oxygen species dynamics. Upon cellular stress, it can be released into the cytosol, where it interacts with apoptotic peptidase activator 1 (APAF1) to form the apoptosome, initiating caspase-dependent apoptotic cell death. Additionally, following exposure to pro-apoptotic compounds, cytochrome c contributes to the survival of drug-tolerant persister cells. When translocated to the nucleus, it can induce chromatin condensation and disrupt nucleosome assembly. Upon its release into the extracellular space, cytochrome c may act as an immune mediator during cell death processes, highlighting its multifaceted role in cellular biology. In this review, we explore the diverse structural and functional aspects of cytochrome c in physiological and pathological responses. We summarize how posttranslational modifications of cytochrome c (e.g., phosphorylation, acetylation, tyrosine nitration, and oxidation), binding proteins (e.g., HIGD1A, CHCHD2, ITPR1, and nucleophosmin), and mutations (e.g., G41S, Y48H, and A51V) affect its function. Furthermore, we provide an overview of the latest advanced technologies utilized for detecting cytochrome c, along with potential therapeutic approaches related to this protein. These strategies hold tremendous promise in personalized health care, presenting opportunities for targeted interventions in a wide range of conditions, including neurodegenerative disorders, cardiovascular diseases, and cancer.

氧化还原活性蛋白细胞色素c是一种带高正电荷的血红蛋白，可调节细胞的生死命运。正常生理条件下，细胞色素c定位于线粒体膜间隙，在特定病理或应激诱导条件下，其分布可延伸至细胞质、细胞核和细胞外间隙。在线粒体中，细胞色素c作为电子传递链中的电子载体，促进三磷酸腺苷合成、调节心磷脂过氧化并影响活性氧动态。在细胞应激时，它可以释放到细胞质中，与凋亡肽酶激活剂 1 (APAF1) 相互作用形成凋亡体，启动 caspase 依赖性细胞凋亡。此外，在接触促凋亡化合物后，细胞色素c有助于耐药持久细胞的存活。当转移到细胞核时，它可以诱导染色质浓缩并破坏核小体组装。细胞色素c释放到细胞外空间后，可能在细胞死亡过程中充当免疫介质，突显了其在细胞生物学中的多方面作用。在这篇综述中，我们探讨了细胞色素c在生理和病理反应中的不同结构和功能。我们总结了细胞色素c（例如磷酸化、乙酰化、酪氨酸硝化和氧化）、结合蛋白（例如 HIGD1A、CHCHD2、ITPR1 和核磷蛋白）和突变（例如 G41S、Y48H 和 A51V）的翻译后修饰如何影响它的功能。此外，我们概述了用于检测细胞色素c的最新先进技术，以及与该蛋白质相关的潜在治疗方法。这些策略在个性化医疗保健方面具有巨大的前景，为神经退行性疾病、心血管疾病和癌症等多种疾病的针对性干预提供了机会。