https://ror.org/024z2rq82 Institute of Biochemistry and Molecular Biology I, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
https://ror.org/024z2rq82 Center for Advanced Imaging, Faculty of Mathematics and Natural Sciences, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Life Sci Alliance. 2023 Nov 13;7(2). doi: 10.26508/lsa.202302386. Print 2024 Feb.
Cristae membranes have been recently shown to undergo intramitochondrial merging and splitting events. Yet, the metabolic and bioenergetic factors regulating them are unclear. Here, we investigated whether and how cristae morphology and dynamics are dependent on oxidative phosphorylation (OXPHOS) complexes, the mitochondrial membrane potential (ΔΨ), and the ADP/ATP nucleotide translocator. Advanced live-cell STED nanoscopy combined with in-depth quantification were employed to analyse cristae morphology and dynamics after treatment of mammalian cells with rotenone, antimycin A, oligomycin A, and CCCP. This led to formation of enlarged mitochondria along with reduced cristae density but did not impair cristae dynamics. CCCP treatment leading to ΔΨ abrogation even enhanced cristae dynamics showing its ΔΨ-independent nature. Inhibition of OXPHOS complexes was accompanied by reduced ATP levels but did not affect cristae dynamics. However, inhibition of ADP/ATP exchange led to aberrant cristae morphology and impaired cristae dynamics in a mitochondrial subset. In sum, we provide quantitative data of cristae membrane remodelling under different conditions supporting an important interplay between OXPHOS, metabolite exchange, and cristae membrane dynamics.
嵴膜最近被证明会发生线粒体内部融合和分裂事件。然而,调节它们的代谢和生物能量因素尚不清楚。在这里,我们研究了嵴的形态和动力学是否以及如何依赖于氧化磷酸化(OXPHOS)复合物、线粒体膜电位(ΔΨ)和 ADP/ATP 核苷酸转位酶。先进的活细胞 STED 纳米显微镜结合深入的定量分析,用于分析哺乳动物细胞用鱼藤酮、抗霉素 A、寡霉素 A 和 CCCP 处理后嵴的形态和动力学。这导致形成了增大的线粒体,同时嵴密度降低,但不损害嵴的动力学。导致 ΔΨ 消除的 CCCP 处理甚至增强了嵴的动力学,表明其具有 ΔΨ 独立性。OXPHOS 复合物的抑制伴随着 ATP 水平的降低,但不影响嵴的动力学。然而,ADP/ATP 交换的抑制导致线粒体亚群中嵴的形态异常和嵴动力学受损。总之,我们提供了不同条件下嵴膜重塑的定量数据,支持 OXPHOS、代谢物交换和嵴膜动力学之间的重要相互作用。