线粒体源性硫化氢及其对线粒体功能的影响

Mitochondrial hydrogen sulfide and its effect on mitochondrial function

摘要:

作为继一氧化氮(NO)和一氧化碳(CO)之外的第三个气体信号分子,硫化氢(H₂S)被证实具有舒张血管、保护神经系统、调节昼夜节律以及抗衰老等多种生物学效应。近来研究发现,细胞质中除了由胱硫醚-β-合酶(CBS)和胱硫醚-γ-裂解酶(CGL或CSE)介导的H₂S合成方式之外,还存在独立的线粒体途径的H₂S合成方式。已有报道证实线粒体靶向的H₂S供体AP39和AP123较经典的无机盐供体NaHS显示出更强的细胞保护作用和更少的细胞毒性,揭示了线粒体源性H₂S作用的特殊性。本文重点介绍线粒体中H₂S的生成与代谢、H₂S对线粒体功能的影响以及新型线粒体靶向H₂S供体的研究进展,以期对H₂S的功能提供更加全面的认识。

Abstract:

Hydrogen sulfide (H₂S) is now recognized as the third “gasotransmitters” along with nitric oxide (NO) and carbon monoxide (CO) and has been proved to have many biological effects, such as vasodilation, neuroprotection, circadian rhythm regulation and anti-aging. Recent studies have revealed an independent mitochondrial H₂S synthesis pathway, which is different from the cytoplasmic H₂S synthesis mediated by cystathionine beta synthase (CBS) and cystathionine gamma lyase (CGL or CSE). It has been reported that two mitochondrial targeted H₂S donors AP39 and AP123 show stronger cell protection and less cytotoxicity than classical inorganic salt donor NaHS, indicating the particularity of mitochondrial H₂S. This review mainly introduced mitochondrial H₂S about its generation, metabolism and effects on mitochondria. Recent progress of the new mitochondrial targeting H₂S donors are also discussed in this paper, in order to provide a more comprehensive understanding of hydrogen sulfide.