bims-miptne Biomed News
on Mitochondrial permeability transition pore-dependent necrosis
Issue of 2025–01–05
two papers selected by
Oluwatobi Samuel Adegbite, University of Liverpool
  1. Mechanisms of postischemic cardiac death and protection following myocardial injury.
  2. Pan-cancer association of a mitochondrial function score with genomic alterations and clinical outcome.
  1. J Clin Invest. 2025 Jan 02. pii: e184134. [Epub ahead of print]135(1):
    Mechanisms of postischemic cardiac death and protection following myocardial injury.
    Yusuf Mastoor, Elizabeth Murphy, Barbara Roman.
      Acute myocardial infarction (MI) is a leading cause of death worldwide. Although with current treatment, acute mortality from MI is low, the damage and remodeling associated with MI are responsible for subsequent heart failure. Reducing cell death associated with acute MI would decrease the mortality associated with heart failure. Despite considerable study, the precise mechanism by which ischemia and reperfusion (I/R) trigger cell death is still not fully understood. In this Review, we summarize the changes that occur during I/R injury, with emphasis on those that might initiate cell death, such as calcium overload and oxidative stress. We review cell-death pathways and pathway crosstalk and discuss cardioprotective approaches in order to provide insight into mechanisms that could be targeted with therapeutic interventions. Finally, we review cardioprotective clinical trials, with a focus on possible reasons why they were not successful. Cardioprotection has largely focused on inhibiting a single cell-death pathway or one death-trigger mechanism (calcium or ROS). In treatment of other diseases, such as cancer, the benefit of targeting multiple pathways with a "drug cocktail" approach has been demonstrated. Given the crosstalk between cell-death pathways, targeting multiple cardiac death mechanisms should be considered.
    DOI:  https://doi.org/10.1172/JCI184134
  2. Sci Rep. 2024 Dec 28. 14(1): 31430
    Pan-cancer association of a mitochondrial function score with genomic alterations and clinical outcome.
    Shikun Zhu, Chen Chen, Min Wang, Yue Liu, Baolin Li, Xing Qi, Miao Song, Xuexue Liu, Jia Feng, Jinbo Liu.
      Mitochondria are pivotal in cellular energy metabolism and have garnered significant attention for their roles in cancer progression and therapy resistance. Despite this, the functional diversity of mitochondria across various cancer types remains inadequately characterized. This study seeks to fill this knowledge gap by introducing and validating MitoScore-a novel metric designed to quantitatively assess mitochondrial function across a wide array of cancers. Our investigation evaluates the capacity of MitoScore not only to distinguish between tumor and adjacent normal tissues but also to serve as a predictive marker for clinical outcomes. We analyzed gene expression data from 24 cancer types and corresponding normal tissues using the TCGA database. MitoScore was calculated by summing the normalized expression levels of six mitochondrial genes known to be consistently altered across multiple cancers. Differential gene expression was assessed using DESeq2, with a focus on identifying significant changes in mitochondrial function. MitoScore's associations with tumor proliferation, hypoxia, aneuploidy, and clinical outcomes were evaluated using Spearman's correlation, linear regression, and Kaplan-Meier survival analyses. MitoScore was significantly higher in tumor tissues compared to normal tissues across most cancer types (p < 0.001). It positively correlated with tumor proliferation rates (r = 0.46), hypoxia scores (r = 0.61), and aneuploidy (r = 0.44), indicating its potential as a marker of aggressive tumor behavior. High MitoScore was also associated with poorer prognosis in several cancer types, suggesting its utility as a predictive biomarker for clinical outcomes. This study introduces MitoScore, a metric for mitochondrial activity often elevated in tumors and linked to poor prognosis. It correlates positively with hypoxia and negatively with stromal and immune infiltration, highlighting mitochondria's role in the tumor microenvironment. MitoScore's association with genomic instability, such as aneuploidy, suggests mitochondrial dysfunction contributes to cancer progression. Despite challenges in mitochondrial-targeted therapies, MitoScore may identify tumors responsive to such treatments, warranting further research for clinical application.
    DOI:  https://doi.org/10.1038/s41598-024-83022-1
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