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Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis

Mol Cell. 2023-12; 
Xiaojian Shi, Marisa DeCiucis, Kariona A Grabinska, Jean Kanyo, Adam Liu, Tukiet T Lam, Hongying Shen
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Catalog Peptides … Indeed, we first identified that human A39 protein level is extremely low in comparison with … 60 ml of TBS buffer containing 300mg/ml FLAG peptide (GenScript, RP10586) after a 20-min … Get A Quote

摘要

Organelle transporters define metabolic compartmentalization, and how this metabolite transport process can be modulated is poorly explored. Here, we discovered that human SLC25A39, a mitochondrial transporter critical for mitochondrial glutathione uptake, is a short-lived protein under dual regulation at the protein level. Co-immunoprecipitation mass spectrometry and CRISPR knockout (KO) in mammalian cells identified that mitochondrial m-AAA protease AFG3L2 is responsible for degrading SLC25A39 through the matrix loop 1. SLC25A39 senses mitochondrial iron-sulfur cluster using four matrix cysteine residues and inhibits its degradation. SLC25A39 protein regulation is robust in developing and mature neurons. This... More

关键词

AFG3L2, SLC25A39, glutathione, iron, mitochondrial transporter, protein quality control