研究人员表示，细胞对线粒体毒物的反应是迅速激活单磷酸腺苷激活的蛋白激酶（AMPK），通过磷酸化引起急性代谢变化，并通过转录作用延长代谢的适应期。转录因子EB（TFEB）是AMPK的一个主要效应器，它能增加溶酶体基因的表达以应对能量压力，但AMPK如何激活TFEB仍未解决。
研究人员证明AMPK直接磷酸化folliculin-interacting protein 1（FNIP1）中五个保守的丝氨酸残基，从而抑制folliculin（FLCN）-FNIP1复合物的功能。FNIP1的磷酸化是AMPK诱导TFEB的核易位和TFEB依赖性地增加过氧化物酶增殖体激活受体伽马协同激活剂1-α（PGC1α）和雌激素相关受体α（ERRα）的信使RNA所需的。因此，线粒体损伤触发了AMPK-FNIP1依赖性的TFEB的核易位，并诱发了溶酶体和线粒体生物生成的连续波。
附：英文原文
Title: Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1
Author: Nazma Malik, Bibiana I. Ferreira, Pablo E. Hollstein, Stephanie D. Curtis, Elijah Trefts, Sammy Weiser Novak, Jingting Yu, Rebecca Gilson, Kristina Hellberg, Lingjing Fang, Arlo Sheridan, Nasun Hah, Gerald S. Shadel, Uri Manor, Reuben J. Shaw
Issue&Volume: 2023-04-21
Abstract: Cells respond to mitochondrial poisons with rapid activation of the adenosine monophosphate–activated protein kinase (AMPK), causing acute metabolic changes through phosphorylation and prolonged adaptation of metabolism through transcriptional effects. Transcription factor EB (TFEB) is a major effector of AMPK that increases expression of lysosome genes in response to energetic stress, but how AMPK activates TFEB remains unresolved. We demonstrate that AMPK directly phosphorylates five conserved serine residues in folliculin-interacting protein 1 (FNIP1), suppressing the function of the folliculin (FLCN)–FNIP1 complex. FNIP1 phosphorylation is required for AMPK to induce nuclear translocation of TFEB and TFEB-dependent increases of peroxisome proliferator–activated receptor gamma coactivator 1-alpha (PGC1α) and estrogen-related receptor alpha (ERRα) messenger RNAs. Thus, mitochondrial damage triggers AMPK-FNIP1–dependent nuclear translocation of TFEB, inducing sequential waves of lysosomal and mitochondrial biogenesis.
DOI: abj5559
Source: https://www.science.org/doi/10.1126/science.abj5559