Knuppertz Laura, Osiewacz Heinz D
Institute of Molecular Biosciences and Cluster of Excellence 'Macromolecular Complexes', Department of Biosciences, J. W. Goethe University, Frankfurt, Germany.
Aging Cell. 2017 Aug;16(4):704-715. doi: 10.1111/acel.12600. Epub 2017 Apr 27.
The degradation of nonfunctional mitochondrial proteins is of fundamental relevance for maintenance of cellular homeostasis. The heteromeric CLPXP protein complex in the mitochondrial matrix is part of this process. In the fungal aging model Podospora anserina, ablation of CLPXP leads to an increase in healthy lifespan. Here, we report that this counterintuitive increase depends on a functional autophagy machinery. In PaClpXP mutants, autophagy is involved in energy conservation and the compensation of impairments in respiration. Strikingly, despite the impact on mitochondrial function, it is not mitophagy but general autophagy that is constitutively induced and required for longevity. In contrast, in another long-lived mutant ablated for the mitochondrial PaIAP protease, autophagy is neither induced nor required for lifespan extension. Our data provide novel mechanistic insights into the capacity of different forms of autophagy to compensate impairments of specific components of the complex mitochondrial quality control network and about the biological role of mitochondrial CLPXP in the control of cellular energy metabolism.
非功能性线粒体蛋白的降解对于维持细胞内稳态至关重要。线粒体基质中的异源CLPXP蛋白复合物是这一过程的一部分。在真菌衰老模型嗜热栖热放线菌中，CLPXP的缺失导致健康寿命延长。在此，我们报道这种违反直觉的寿命延长依赖于功能性自噬机制。在PaClpXP突变体中，自噬参与能量守恒和呼吸功能障碍的补偿。令人惊讶的是，尽管对线粒体功能有影响，但长寿所必需且持续诱导的不是线粒体自噬而是一般自噬。相比之下，在另一个因线粒体PaIAP蛋白酶缺失而长寿的突变体中，自噬既不被诱导，也不是寿命延长所必需的。我们的数据为不同形式的自噬补偿复杂线粒体质量控制网络特定组分损伤的能力以及线粒体CLPXP在细胞能量代谢控制中的生物学作用提供了新的机制见解。
