Mitochondrial translation elongation controls OXPHOS biogenesis by coordinating synthesis and folding of mitochondrially encoded proteins PMID: 41997111

ADC Targets in Oncology

2026-04-10

Mitochondrial translation elongation controls OXPHOS biogenesis by coordinating synthesis and folding of mitochondrially encoded proteins

Mol Cell. 2026 Apr 16;86(8):1511-1528.e12. doi: 10.1016/j.molcel.2026.03.017.

Lvxin Xie ¹ , Shuchao Ren ¹ , Li Zhang ¹ , Ziqing Wang ¹ , Tong Wu ² , Qing Dai ² , Shikun Xiang ³ , Zhihua Qian ⁴ , Yufan Xian ¹ , Shutong Xu ⁴ , Xiao-Lin Chen ³ , Chuan He ⁵ , Yi Liu ⁶ , Zhipeng Zhou ⁷

Affiliations

1. National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
2. Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
3. National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Provincial Key Laboratory of Plant Pathology of Hubei Province, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
4. National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Hongshan Laboratory, Wuhan, Hubei, 430070, China.
5. Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
6. Department of Physiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
7. National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, 430070, China. Electronic address: [email protected].

Abstract

Mitochondria generate ATP through Oxidative Phosphorylation (OXPHOS), with core structural subunits encoded by mitochondrial DNA (mtDNA) and translated by mitochondrial ribosomes. However, how mitochondrial translation elongation influences OXPHOS biogenesis remains unclear. Here, we show that in Neurospora crassa, the mitochondrial ribosomal RNA (rRNA) methyltransferase 1 (MRM1) promotes OXPHOS biogenesis by repressing translation elongation independently of its catalytic activity. The N-terminal intrinsically disordered region (IDR) of MRM1 binds simultaneously to mitochondrial ribosomes and mRNAs. Disrupting either interaction accelerates elongation and enhances synthesis of mtDNA-encoded OXPHOS subunits but impairs their co-translational folding and membrane insertion. Pharmacological slowing of mitochondrial translation partially alleviates these defects. The MRM1 IDR is conserved in Ascomycete fungi and is essential for plant Infection by Magnaporthe oryzae. Together, our findings identify translation elongation control as a mechanism coordinating mitochondrial protein synthesis and folding during OXPHOS biogenesis and MRM1 as a potential target for broad-spectrum Antifungal strategies.

Keywords

Magnaporthe oryzae; Neurospora crassa; mitochondrial rRNA methyltransferase; mitochondrial translation; oxidative phosphorylation; protein folding; translation elongation.