bims-mitpro 2026-08-30 papers

Genetics. 2026 Aug 26. pii: iyag203. [Epub ahead of print]

Traffic jam at the powerhouse: restoring protein homeostasis at the mitochondria via MFB1 and HSP31 collaboration with clinical implications. An Educational Primer for use with "Cellular proteostasis during mitochondrial protein import clogging requires the mitochondrial F-box protein 1 and DJ-1 homolog HSP31 in Saccharomyces cerevisiae".

Mahima Ghosh, Patricia Melloy.

Keywords: AAC2 ; HSP31 ; MFB1 ; budding yeast; cytotoxicity; mitochondrial protein import; proteostasis

DOI: https://doi.org/10.1093/genetics/iyag203

Autophagy. 2026 Aug 28.

A New agent in the matrix: PINK1's expanded role in mitochondrial surveillance and Regulation.

Ian Collinson, Robin A Corey, Adam G Grieve.

The identification of pathogenic autosomal recessive mutations in the gene encoding the PINK1 kinase provided early evidence linking mitochondrial dysfunction to neurodegeneration - in this case Parkinson's Disease. PINK1 has since become synonymous with mitophagy, with the prevailing model proposing two alternative fates. The first being partial import - inner-membrane penetration of its transmembrane domain (TMD) - followed by PARL-mediated cleavage and degradation. This happens in healthy mitochondria with a high membrane potential (ΔΨ) across the inner-membrane - required for passage of proteins into or across the inner-membrane. The second being surface stabilization, Parkin activation and initiation of mitophagy upon membrane depolarization. But what if PINK1 acts in active mitochondria as well? Our recent work identifies a third fate - matrix entry! The findings expand the biology of PINK1 beyond mitochondrial surveillance for quality control alone. They suggest an additional mitophagy-independent regulatory role within the matrix, which turns out to be governed by the unusual properties of its TMD for the conferral of a decisive conformational switch.

Keywords: Mitochondria; PARL; PINK1; Parkinson’s disease; transmembrane

DOI: https://doi.org/10.1080/15548627.2026.2726091

Biochem Soc Trans. 2026 Sep 23. 54(9): 1155-1167

The molecular mechanisms of crista formation: how mitochondria give themselves breathing room.

Lilia Colina-Tenorio, Martina Bohuslavová, Alexander W Bruce, Hassan Hashimi.

Cristae are mitochondrial subcompartments that give the organelle its distinctive appearance. More significantly, mitochondria are the proverbial powerhouses as cristae house the molecular machinery underlying cellular respiration, a process that converts carbon sources into ATP by chemiosmosis. The form of cristae is invariably connected to their bioenergetic function. Here, we review our current understanding of the molecules underpinning crista formation. Not surprisingly, respiratory chain multiprotein complexes are involved in crista formation, with F1FO-ATP synthase dimers being eminent membrane sculptors. But crista formation also requires factors that are not directly part of the respiratory chain. The most ancient is the MICOS complex, which delineates the subcompartment and acts as a hub for crista biogenesis. The mitochondrial inner membrane (IM), from which cristae emerge, is remodelled by different dynamin-related proteins in animals and fungi. Cardiolipin is an integral component of the membranous fabric of the IM. To begin to grasp general design principles underlying crista formation, we synthesize findings from canonical animal and yeast experimental models with those from diverse protists and other eukaryotes. However, how these molecules are orchestrated during crista formation remains a hidden piece in our understanding of how cells differentiate in specialized forms. We highlight the few knowns about crista formation in a handful of organisms to guide research into the many unknowns about how complex subcompartments represented by mitochondrial cristae are formed.

Keywords: ATP synthase; MICOS; cristae; dynamin-related protein; mitochondria; oxidative phosphorylation

DOI: https://doi.org/10.1042/BST20260167

Mitochondrion. 2026 Aug 22. pii: S1567-7249(26)00095-4. [Epub ahead of print]91 102205

Loss of mitochondrial co-chaperone GRPEL2 protects mice from age- and diet-induced obesity.

Yang Yang, Nirajan Neupane, Jouni Kvist, Jonna Saarimäki-Vire, Matthias Schewe, Kalle Luopajärvi, Pooja Manjunath, Svetlana Konovalova, Rubén Torregrosa-Muñumer, Veijo Kinnunen, Pekka Katajisto, Timo Otonkoski, Eija Pirinen, Jayasimman Rajendran, Henna Tyynismaa.

Mitochondrial protein homeostasis intersects with metabolic control, but the in vivo roles of specific mitochondrial co-chaperones remain unclear. The chaperone mtHSP70 plays a key role in import and folding of nuclear-encoded proteins targeted to mitochondrial matrix. Its protein folding cycle is regulated by the GrpE-like nucleotide exchange factor GRPEL1. Vertebrates also have a GRPEL2 paralog, postulated as the stress-sensitive counterpart, but its physiological relevance is not known. We show here that GRPEL2 is not essential for viability in mice, and its absence does not induce proteotoxic stress responses in stark contrast to GRPEL1. However, we find that GRPEL2 has a role in regulating body weight homeostasis. GRPEL2 knockout mice are protected from age- and diet-induced weight gain and maintain a better metabolic health and insulin sensitivity. Transcriptional profiling revealed minimal changes in liver and skeletal muscle, whereas white adipose tissue from Grpel2-deficient mice lacked the obesity-associated remodeling seen in controls. We propose that GRPEL2 fine-tunes metabolic setpoints without broadly perturbing mitochondrial protein import, thereby maintaining adipose tissue health during nutritional excess. These findings show that subtle alterations in mitochondrial chaperone systems reshape systemic metabolism and could suggest strategies to mitigate obesity and insulin resistance through targeted modulation of mitochondrial proteostasis.

Keywords: Adipose tissue; Body weight homeostasis; Grpel2; Mitochondrial protein import; Nucleotide exchange factor; mtHSP70

DOI: https://doi.org/10.1016/j.mito.2026.102205