bims-mithem Biomed News
on Mitochondria in Hematopoiesis
Issue of 2025–10–19
two papers selected by
Tim van Tienhoven, Erasmus Medical Center
  1. The mitochondrial side of frailty.
  2. From Biogenesis to Breakdown: How Protein Biogenesis and Quality Control Failures Drive Mitochondrial Disease.
  1. Curr Opin Clin Nutr Metab Care. 2025 Oct 06.
    The mitochondrial side of frailty.
    Emanuele Marzetti, Rosa Di Lorenzo, Anna Picca.
       PURPOSE OF REVIEW: Frailty, a prevalent geriatric condition marked by reduced physiological reserve and greater vulnerability to stressors, is increasingly linked to mitochondrial dysfunction. This review summarizes current evidence on mitochondrial quality control, bioenergetics, and signaling in frailty, with emphasis on biomarker discovery and translational potential.
    RECENT FINDINGS: Preclinical and human studies have shown that impaired mitochondrial biogenesis, altered dynamics, and defective mitophagy contribute to frailty, sarcopenia, and immune dysregulation. Frail older adults exhibit reduced mitochondrial DNA content, diminished mitochondrial respiratory capacity, elevated reactive oxygen species generation, and distinctive metabolomic changes. Potential biomarkers include mitochondria-derived vesicles, circulating metabolites, and measures of peripheral blood mononuclear cell respiration, which may enable early detection of functional decline. Multivariate profiling approaches have identified sex-specific and shared molecular signatures converging on mitochondrial pathways. Interventions promoting mitochondrial health, including resistance training and targeted immunomodulation, hold promise in slowing frailty progression.
    SUMMARY: Mitochondrial dysfunction lies at the intersection of musculoskeletal, metabolic, and immune changes underpinning frailty. While integrative biomarker panels have defined metabolic signatures, early diagnosis and personalized therapies remain unmet needs. Longitudinal studies are required to establish causality, refine biomarker utility, and guide precision medicine strategies to preserve mitochondrial function, extend healthspan, and improve quality of life in aging populations.
    Keywords:  inflammaging; metabolic dysregulation; mitochondrial quality control; oxidative capacity; physical frailty
    DOI:  https://doi.org/10.1097/MCO.0000000000001175
  2. Mol Cell Biol. 2025 Oct 17. 1-27
    From Biogenesis to Breakdown: How Protein Biogenesis and Quality Control Failures Drive Mitochondrial Disease.
    Phoebe J Leeming, Julia Mercuri-Svik, Diana Stojanovski.
      Mitochondria rely on the coordinated function of over 1000 proteins, most of which are nuclear-encoded, synthesized in the cytosol, and imported into distinct mitochondrial sub-compartments. Thirteen additional proteins are synthesized within the organelle itself, forming core components of the oxidative phosphorylation (OXPHOS) system. Once inside, mitochondrial precursors undergo precise maturation, folding, and assembly, supported by specialized factors that ensure their function. These processes are safeguarded by an intricate network of chaperones, proteases, and disaggregases that maintain proteome integrity. Protein biogenesis and quality control are deeply interconnected, operating continuously to preserve mitochondrial function. Disruption at any stage, whether in import, folding, assembly, or degradation, can lead to proteotoxic stress and mitochondrial dysfunction, underlying a wide spectrum of mitochondrial diseases. Despite progress in characterizing many of these pathways in human cells, large gaps in knowledge remain. A complete understanding of protein biogenesis and surveillance mechanisms is essential to uncover how their dysregulation drives disease. This knowledge will be foundational for interpreting pathogenic mutations, predicting disease mechanisms, and ultimately guiding therapeutic strategies aimed at restoring mitochondrial proteostasis and health.
    Keywords:  Mitochondria; mitochondrial disease; protein import; protein quality control
    DOI:  https://doi.org/10.1080/10985549.2025.2566671
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