Park Na Yeon, Cho Dong-Hyung
Organelle Institute, Kyungpook National University, Daegu, Republic of Korea.
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.
Autophagy. 2025 Mar 24:1-2. doi: 10.1080/15548627.2025.2479669.
Lysophagy, the selective macroautophagic/autophagic clearance of damaged lysosomes, is a critical mechanism for maintaining cellular homeostasis. Our recent study identified a novel regulatory axis involving TBK1, SCF, TMEM192, and TAX1BP1 that orchestrates lysophagic flux following lysosomal damage. We demonstrated that TBK1-dependent phosphorylation of FBXO3 facilitates its interaction with TMEM192, promoting its ubiquitination and subsequent recognition by the autophagy receptor TAX1BP1. Perturbing this pathway significantly reduces lysophagic flux and results in accumulation of damaged lysosomes. These findings establish a previously unrecognized mechanistic link between ubiquitination, receptor recruitment, and lysophagic degradation, broadening our understanding of lysosomal quality control.
溶酶体自噬是指对受损溶酶体进行选择性巨自噬/自噬清除，是维持细胞内稳态的关键机制。我们最近的研究确定了一个涉及TBK1、SCF、TMEM192和TAX1BP1的新型调控轴，该调控轴在溶酶体受损后协调溶酶体自噬通量。我们证明，TBK1依赖的FBXO3磷酸化促进其与TMEM192的相互作用，促进其泛素化以及随后被自噬受体TAX1BP1识别。干扰该途径会显著降低溶酶体自噬通量，并导致受损溶酶体的积累。这些发现建立了泛素化、受体募集和溶酶体自噬降解之间以前未被认识的机制联系，拓宽了我们对溶酶体质量控制的理解。
