Fructose directly remodels the TOM complex to impair oxidative phosphorylation in podocytes

This study demonstrated that, in addition to the known metabolic effects of fructose, excessive fructose directly binds to the translocase of the outer membrane (TOM) complex via non-covalent interaction with TOM22, inducing subtle but functionally critical conformational changes in the TOM complex. These changes markedly inhibit the transport of mitochondrial ribosome subunits, impair mitochondrial protein translation, and disrupt oxidative phosphorylation, independent of fructose metabolism. Using both fructose-exposed podocytes and mouse glomerular injury models, the authors further showed that disrupting the fructose-TOM22 interaction restores mitochondrial ribosome subunit trafficking and prevents mitochondrial and oxidative phosphorylation dysfunction, thereby revealing a previously unrecognized, metabolism-independent pathogenic mechanism by which fructose directly remodels a mitochondrial protein complex to drive mitochondrial dysfunction.本研究证实，除已明确的果糖代谢效应外，过量果糖可通过与TOM22发生非共价相互作用，直接结合外膜转位酶（translocase of the outer membrane，TOM）复合物，并诱导该复合物产生细微但功能关键的构象变化。此类变化可显著抑制线粒体核糖体亚基的转运过程，损害线粒体蛋白质翻译，并破坏氧化磷酸化，且该效应不依赖果糖的代谢通路。研究人员通过果糖暴露的足细胞与小鼠肾小球损伤模型进一步验证，阻断果糖与TOM22的相互作用可恢复线粒体核糖体亚基的转运功能，改善线粒体功能与氧化磷酸化紊乱。据此，本研究揭示了一种此前未被认知的、不依赖代谢途径的致病机制：果糖可直接重塑线粒体蛋白质复合物，进而诱发线粒体功能障碍。

搜集汇总

背景与挑战

背景概述

该数据集源自一项蛋白质组学研究，揭示了果糖通过非共价结合线粒体外膜转位酶复合物（TOM）的TOM22亚基，直接改变其构象，从而抑制线粒体核糖体亚基转运并损害氧化磷酸化，这是一种独立于代谢的新致病机制。数据集包含8.7GB的实验数据，由南京大学的研究人员创建，并以CC0许可公开共享，支持对果糖诱导足细胞线粒体功能障碍的深入研究。