Hoyer Melissa J, Swarup Sharan, Harper J Wade
Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, Boston MA 02115, USA.
Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Curr Opin Physiol. 2022 Oct;29. doi: 10.1016/j.cophys.2022.100590. Epub 2022 Aug 30.
Lysosomes are subjected to physiological and patho-physiological insults over the course of their life cycle and are accordingly repaired or recycled. Lysophagy, the selective degradation of lysosomes via autophagy, occurs upon unrepairable lysosomal membrane rupture; galectins bind to glycosylated macromolecules in the lysosome lumen, orchestrating a series of cellular responses to promote autophagic recycling of damaged lysosomes and transcriptional upregulation of lysosomal genes. Damaged lysosomes are ubiquitylated, resulting in the recruitment of ubiquitin-binding autophagy receptors, which promote assembly of an autophagosome around damaged lysosomes for delivery to healthy lysosomes for degradation. Here, we review the current state of our understanding of mechanisms used to mark and eliminate damaged lysosomes, and discuss the complexities of galectin function and ubiquitin-chain linkage types. Finally, we discuss the limitations of available data and challenges with the goal of understanding the mechanistic basis of key steps in lysophagic flux.
溶酶体在其生命周期中会受到生理和病理生理损伤，因此会被修复或再循环利用。当溶酶体膜发生不可修复的破裂时，会发生溶酶体自噬，即通过自噬选择性降解溶酶体；半乳糖凝集素与溶酶体腔内的糖基化大分子结合，协调一系列细胞反应，以促进受损溶酶体的自噬再循环和溶酶体基因的转录上调。受损的溶酶体会被泛素化，导致泛素结合自噬受体的募集，这些受体促进自噬体围绕受损溶酶体组装，以便将其递送至健康的溶酶体进行降解。在这里，我们综述了目前对用于标记和消除受损溶酶体的机制的理解现状，并讨论了半乳糖凝集素功能和泛素链连接类型的复杂性。最后，我们讨论现有数据的局限性和挑战，旨在理解溶酶体自噬通量关键步骤的机制基础。
