bims-mitpro 2026-04-19 papers

Issue of 2026–04–19
three papers selected by
Andreas Kohler, Umeå University

J Cell Sci. 2026 Apr 13. pii: jcs.264577. [Epub ahead of print]

A ULK1-MTFR1L feedback loop links mitochondrial fission, mitophagy and apoptosis.

Riccardo Babic, Leon Lucya, Christoph Reiter, Franziska Kriegenburg, Ramón Castellanos-Martínez, David M Hollenstein, Florian Becker, Carola Hunte, Claudine Kraft.

Mitophagy, the selective degradation of damaged mitochondria, preserves mitochondrial quality, yet how mitochondrial fission is coordinated with autophagy initiation remains unclear. Here we identify the mitochondrial outer membrane protein MTFR1L as a key component of mitophagy initiation hubs after using a synthetic FKBP-FRB system to tether ULK1 kinase to mitochondria independently of damage. We find that MTFR1L is enriched at ULK1 foci together with additional fission factors and constitutive mitochondrial targeting of MTFR1L shifts mitochondrial morphology towards fragmentation. MTFR1L depletion decreases respiratory capacity, elevates apoptosis, and impairs mitophagy flux. Upon mitophagy induction, MTFR1L is phosphorylated in a ULK1 kinase-dependent manner, and reciprocally modulates ULK1 activity, establishing a feedback loop. Moreover, MTFR1L is required for proper ATG13 stability. These findings position MTFR1L as a critical link between mitochondrial fission and the autophagy machinery, coordinating mitophagy initiation and cell survival.

Keywords: ATG13; Autophagy; MTFR1L; Mitophagy; ULK1

DOI: https://doi.org/10.1242/jcs.264577

Trends Biochem Sci. 2026 Apr 16. pii: S0968-0004(26)00061-7. [Epub ahead of print]

Molecular mechanisms of PINK1/Parkin-mediated mitochondrial quality control.

Andrew N Bayne, Jean-François Trempe.

PINK1/Parkin-mediated mitophagy and other related mitochondrial quality control pathways are critical to maintaining cellular homeostasis and neuronal health, and indeed, mutations in PINK1 and PRKN that disrupt this pathway cause early-onset Parkinson's disease. While PINK1-dependent Parkin recruitment to damaged mitochondria has been established for over a decade, recent structural and biochemical advances have illuminated the mechanisms governing their allosteric activation and integration into broader cellular signaling networks. This review synthesizes these insights, focusing on the molecular determinants of PINK1/Parkin activation and the regulatory crosstalk that integrates mitophagy with other cellular stress responses. These mechanistic advances position the PINK1/Parkin pathway as a promising, tractable therapeutic target for Parkinson's disease and related pathologies.

Keywords: PINK1; Parkin; Parkinson’s disease; mitochondrial quality control (MQC); mitophagy; stress response; therapeutic development

DOI: https://doi.org/10.1016/j.tibs.2026.02.014

Mol Cell. 2026 Apr 16. pii: S1097-2765(26)00193-0. [Epub ahead of print]86(8): 1511-1528.e12

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

Lvxin Xie, Shuchao Ren, Li Zhang, Ziqing Wang, Tong Wu, Qing Dai, Shikun Xiang, Zhihua Qian, Yufan Xian, Shutong Xu, Xiao-Lin Chen, Chuan He, Yi Liu, Zhipeng Zhou.

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

DOI: https://doi.org/10.1016/j.molcel.2026.03.017