Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, via Tolara di Sopra, 50, 40064, Ozzano Emilia, Bologna, Italy.
Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, via Tolara di Sopra, 50, 40064, Ozzano Emilia, Bologna, Italy.
Biochimie. 2021 Jan;180:222-228. doi: 10.1016/j.biochi.2020.11.012. Epub 2020 Nov 17.
The molecular mechanisms which rule the formation and opening of the mitochondrial permeability transition pore (mPTP), the lethal mechanism which permeabilizes mitochondria to water and solutes and drives the cell to death, are still unclear and particularly little investigated in invertebrates. Since Ca increase in mitochondria is accompanied by mPTP opening and the participation of the mitochondrial FF-ATPase in the mPTP is increasingly sustained, the substitution of the natural cofactor Mg by Ca in the FF-ATPase activation has been involved in the mPTP mechanism. In mussel midgut gland mitochondria the similar kinetic properties of the Mg- or Ca-dependent FF-ATPase activities, namely the same affinity for ATP and bi-site activation kinetics by the ATP substrate, in spite of the higher enzyme activity and coupling efficiency of the Mg-dependent FF-ATPase, suggest that both enzyme activities are involved in the bioenergetic machinery. Other than being a mitochondrial poison and environmental contaminant, sulfide at low concentrations acts as gaseous mediator and can induce post-translational modifications of proteins. The sulfide donor NaHS, at micromolar concentrations, does not alter the two FF-ATPase activities, but desensitizes the mPTP to Ca input. Unexpectedly, NaHS, under the conditions tested, points out a chemical refractoriness of both FF-ATPase activities and a failed relationship between the Ca-dependent FF-ATPase and the mPTP in mussels. The findings suggest that mPTP role and regulation may be different in different taxa and that the FF-ATPase insensitivity to NaHS may allow mussels to cope with environmental sulfide.
调控线粒体通透性转换孔（mPTP）形成和开放的分子机制，即导致线粒体通透性增加和细胞死亡的致死机制，在无脊椎动物中仍然不清楚，特别是研究得很少。由于线粒体中 Ca 增加伴随着 mPTP 的开放，并且线粒体 FF-ATP 酶参与 mPTP 的作用越来越大，因此 FF-ATP 酶激活中天然辅因子 Mg 被 Ca 取代与 mPTP 机制有关。在贻贝中肠腺线粒体中，Mg 或 Ca 依赖性 FF-ATP 酶活性具有相似的动力学特性，即对 ATP 的亲和力相同，并且由 ATP 底物的双位点激活动力学，尽管 Mg 依赖性 FF-ATP 酶的酶活性和偶联效率较高，但这两种酶活性都参与了生物能量机制。除了作为线粒体毒物和环境污染物外，硫化物在低浓度下作为气态介质起作用，并可以诱导蛋白质的翻译后修饰。在微摩尔浓度下，硫化物供体 NaHS 不会改变两种 FF-ATP 酶活性，但使 mPTP 对 Ca 输入脱敏。出乎意料的是，在测试条件下，NaHS 表明贻贝中两种 FF-ATP 酶活性的化学抗性以及 Ca 依赖性 FF-ATP 酶与 mPTP 之间的关系失败。这些发现表明，mPTP 的作用和调节可能在不同的分类群中不同，并且 FF-ATP 酶对 NaHS 的不敏感性可能使贻贝能够应对环境中的硫化物。
