Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Cell Mol Biol Lett. 2024 Jun 4;29(1):85. doi: 10.1186/s11658-024-00597-3.
The molecular basis for bulk autophagy activation due to a deficiency in essential nutrients such as carbohydrates, amino acids, and nitrogen is well understood. Given autophagy functions to reduce surplus to compensate for scarcity, it theoretically possesses the capability to selectively degrade specific substrates to meet distinct metabolic demands. However, direct evidence is still lacking that substantiates the idea that autophagy selectively targets specific substrates (known as selective autophagy) to address particular nutritional needs. Recently, Gross et al. found that during phosphate starvation (P-S), rather than nitrogen starvation (N-S), yeasts selectively eliminate peroxisomes by dynamically altering the composition of the Atg1/ULK kinase complex (AKC) to adapt to P-S. This study elucidates how the metabolite sensor Pho81 flexibly interacts with AKC and guides selective autophagic clearance of peroxisomes during P-S, providing novel insights into the metabolic contribution of autophagy to special nutritional needs.
由于碳水化合物、氨基酸和氮等必需营养素的缺乏而导致的大自噬激活的分子基础已得到很好的理解。由于自噬的功能是减少过剩以弥补不足,因此它理论上具有选择性降解特定底物以满足不同代谢需求的能力。然而,仍然缺乏直接证据来证实自噬能够选择性地靶向特定底物(称为选择性自噬)以满足特定的营养需求。最近,Gross 等人发现,在磷酸盐饥饿(P-S)期间,而不是氮饥饿(N-S)期间,酵母通过动态改变 Atg1/ULK 激酶复合物(AKC)的组成来选择性地消除过氧化物酶体,以适应 P-S。这项研究阐明了代谢物传感器 Pho81 如何灵活地与 AKC 相互作用,并指导 P-S 期间过氧化物酶体的选择性自噬清除,为自噬对特殊营养需求的代谢贡献提供了新的见解。