bims-mitpro 2025-03-02 papers

Autophagy. 2025 Feb 27.

Mitochondrial dynamics and quality control regulate proteostasis in neuronal ischemia-reperfusion.

Garrett M Fogo, Sarita Raghunayakula, Katlynn J Emaus, Francisco J Torres Torres, Gary Shangguan, Joseph M Wider, Maik Hüttemann, Thomas H Sanderson.

Mitochondrial damage and dysfunction are hallmarks of neuronal injury during cerebral ischemia-reperfusion (I/R). Critical mitochondrial functions including energy production and cell signaling are perturbed during I/R, often exacerbating damage and contributing to secondary injury. The integrity of the mitochondrial proteome is essential for efficient function. Mitochondrial proteostasis is mediated by the cooperative forces of mitophagy and intramitochondrial proteolysis. The aim of this study was to elucidate the patterns of mitochondrial protein dynamics and their key regulators during an in vitro model of neuronal I/R injury. Utilizing the MitoTimer reporter, we quantified mitochondrial protein oxidation and turnover during I/R injury, highlighting a key point at 2 h reoxygenation for aged/oxidized protein turnover. This turnover was found to be mediated by both LONP1-dependent proteolysis and PRKN/parkin-dependent mitophagy. Additionally, the proteostatic response of neuronal mitochondria is influenced by both mitochondrial fusion and fission machinery. Our findings highlight the involvement of both mitophagy and intramitochondrial proteolysis in the response to I/R injury.

Keywords: Fission; LONP1; PRKN; fusion; mitophagy; neuron

DOI: https://doi.org/10.1080/15548627.2025.2472586

Biol Cell. 2025 Feb;117(2): e12007

Mitochondrial Ribosome Regulation Drives Spermatogenesis and Male Fertility.

Zhanxin Chang, Long Miao, Peng Wang.

Mitochondria, as the central hub of cellular energy metabolism and a critical regulator of signaling pathways, play indispensable roles in spermatogenesis and sperm function. In recent years, the mechanisms by which RNA-binding proteins regulate reproductive development and gametogenesis have emerged as a focal point in mitochondrial biology. Here, we review the latest progresses on the role of mitochondrial translation and its associated ribosomal regulation in sperm formation and activation. In Caenorhabditis elegans, the RNA-binding protein complex AMG-1/SLRP-1 modulates key processes of sperm development by maintaining mitochondrial homeostasis. Furthermore, we explore the distinct roles of mitochondrial translation and metabolic functions in sperm activation and motility. This review summarizes the mechanisms by which mitochondrial ribosomal regulation governs spermatogenesis and sperm function, offering a foundation for future investigations in reproductive biology.

Keywords: AMG‐1/SLRP‐1 complex; RNA‐binding proteins; male infertility; mitochondrial ribosomes; spermatogenesis

DOI: https://doi.org/10.1111/boc.12007

Nat Metab. 2025 Feb 24.

Mitochondrial superoxide regulates pro-inflammatory macrophages.

DOI: https://doi.org/10.1038/s42255-025-01223-y

Cell Metab. 2025 Feb 20. pii: S1550-4131(25)00017-8. [Epub ahead of print]

MARIGOLD and MitoCIAO, two searchable compendia to visualize and functionalize protein complexes during mitochondrial remodeling.

Mitochondrial proteins assemble dynamically in high molecular weight complexes essential for their functions. We generated and validated two searchable compendia of these mitochondrial complexes. Following identification by mass spectrometry of proteins in complexes separated using blue-native gel electrophoresis from unperturbed, cristae-remodeled, and outer membrane-permeabilized mitochondria, we created MARIGOLD, a mitochondrial apoptotic remodeling complexome database of 627 proteins. MARIGOLD elucidates how dynamically proteins distribute in complexes upon mitochondrial membrane remodeling. From MARIGOLD, we developed MitoCIAO, a mitochondrial complexes interactome tool that, by statistical correlation, calculates the likelihood of protein cooccurrence in complexes. MitoCIAO correctly predicted biologically validated interactions among components of the mitochondrial cristae organization system (MICOS) and optic atrophy 1 (OPA1) complexes. We used MitoCIAO to functionalize two ATPase family AAA domain-containing 3A (ATAD3A) complexes: one with OPA1 that regulates mitochondrial ultrastructure and the second containing ribosomal proteins that is essential for mitoribosome stability. These compendia reveal the dynamic nature of mitochondrial complexes and enable their functionalization.

Keywords: ATAD3A; OPA1; cristae remodeling; interactome; mitochondria; mitochondrial complexes; mitoribosome stability

DOI: https://doi.org/10.1016/j.cmet.2025.01.017