The mitochondrion is a highly dynamic organelle that is critical for energy production and numerous metabolic processes. Drosophila Chchd2, a homolog of the human disease-related genes CHCHD2 and CHCHD10, encodes a mitochondrial protein. In this study, we found that loss of Chchd2 in flies resulted in progressive degeneration of photoreceptor cells and reduced muscle integrity. In the flight muscles of adult Chchd2 mutants, some mitochondria exhibited curling cristae and a reduced number of cristae compared to those of controls. Overexpression of Chchd2 carrying human disease-related point mutations failed to fully rescue the mitochondrial defects in Chchd2 mutants. In fat body cells, loss of Chchd2 resulted in fragmented mitochondria that could be partially rescued by Marf overexpression and enhanced by Opa1 RNAi. The expression level of Opa1 was reduced in Chchd2 mutants and increased when Chchd2 was overexpressed. The chaperone-like protein P32 co-immunoprecipitated with Chchd2 and YME1L, a protease known to processes human OPA1. Moreover, the interaction between P32 and YME1L enhanced YME1L activity and promoted Opa1 degradation. Finally, Chchd2 stabilized Opa1 by competing with P32 for YME1L binding. We propose a model whereby Chchd2 regulates mitochondrial morphology and tissue homeostasis by fine-tuning the levels of OPA1.

中文翻译：

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Chchd2 通过调节 Opa1 的水平来调节线粒体形态。

线粒体是一种高度动态的细胞器，对能量产生和众多代谢过程至关重要。果蝇 Chchd2 是人类疾病相关基因 CHCHD2 和 CHCHD10 的同源物，编码线粒体蛋白。在这项研究中，我们发现果蝇中 Chchd2 的缺失导致感光细胞进行性退化和肌肉完整性降低。在成年 Chchd2 突变体的飞行肌肉中，与对照相比，一些线粒体表现出卷曲的嵴和减少的嵴数量。携带人类疾病相关点突变的 Chchd2 的过度表达未能完全挽救 Chchd2 突变体中的线粒体缺陷。在脂肪体细胞中，Chchd2 的缺失导致线粒体碎片化，Marf 过度表达可以部分挽救这些线粒体，并通过 Opa1 RNAi 增强。Opa1 的表达水平在 Chchd2 突变体中降低，当 Chchd2 过表达时增加。伴侣蛋白 P32 与 Chchd2 和 YME1L（一种已知可处理人类 OPA1 的蛋白酶）共免疫沉淀。此外，P32 和 YME1L 之间的相互作用增强了 YME1L 的活性并促进了 Opa1 的降解。最后，Chchd2 通过与 P32 竞争 YME1L 结合来稳定 Opa1。我们提出了一个模型，其中 Chchd2 通过微调 OPA1 的水平来调节线粒体形态和组织稳态。Chchd2 通过与 P32 竞争 YME1L 结合来稳定 Opa1。我们提出了一个模型，其中 Chchd2 通过微调 OPA1 的水平来调节线粒体形态和组织稳态。Chchd2 通过与 P32 竞争 YME1L 结合来稳定 Opa1。我们提出了一个模型，其中 Chchd2 通过微调 OPA1 的水平来调节线粒体形态和组织稳态。