bims-mionch 2024-05-26 papers

Issue of 2024–05–26
three papers selected by
Gun Kim, Seoul National University

Cell Stress Chaperones. 2024 May 17. pii: S1355-8145(24)00074-9. [Epub ahead of print]

Mitochondrial Chaperone Code: Just Warming Up.

R Felipe Perez, Gianna Mochi, Ariba Khan, Mark Woodford.

More than 99% of the mitochondrial proteome is encoded by the nucleus and requires refolding following import. Therefore, mitochondrial proteins require the coordinated action of molecular chaperones for their folding and activation. Several heat shock protein (Hsp) molecular chaperones, including members of the Hsp27, Hsp40/70, and Hsp90 families, as well as the chaperonin complex Hsp60/10 have an established role in mitochondrial protein import and folding. The 'Chaperone Code' describes the regulation of chaperone activity by dynamic post-translational modifications; however, little is known about post-translational regulation of mitochondrial chaperones. Dissecting the regulation of chaperone function is essential for understanding their differential regulation in pathogenic conditions and the potential development of efficacious therapeutic strategies. Here, we summarize the recent literature on post-translational regulation of mitochondrial chaperones, the consequences for mitochondrial function, and potential implications for disease.

Keywords: chaperones; heat shock proteins; metabolism; mitochondria; post-translational modification

DOI: https://doi.org/10.1016/j.cstres.2024.05.002

Cell Commun Signal. 2024 May 24. 22(1): 285

Molecular mechanisms of aging and anti-aging strategies.

Yumeng Li, Xutong Tian, Juyue Luo, Tongtong Bao, Shujin Wang, Xin Wu.

Aging is a complex and multifaceted process involving a variety of interrelated molecular mechanisms and cellular systems. Phenotypically, the biological aging process is accompanied by a gradual loss of cellular function and the systemic deterioration of multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that aging is closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, loss of nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, loss of protein balance, deregulated nutrient sensing, altered intercellular communication, and dysbiosis. These age-related changes may be alleviated by intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, and targeted longevity genes. In this review, we summarise the key historical progress in the exploration of important causes of aging and anti-aging strategies in recent decades, which provides a basis for further understanding of the reversibility of aging phenotypes, the application prospect of synthetic biotechnology in anti-aging therapy is also prospected.

Keywords: Aging; Aging triggers; Anti-aging strategies; Senolytic; Synthetic

DOI: https://doi.org/10.1186/s12964-024-01663-1

Biochim Biophys Acta Mol Cell Res. 2024 May 20. pii: S0167-4889(24)00095-8. [Epub ahead of print] 119752

Mitophagy at the crossroads of cancer development: Exploring the role of mitophagy in tumor progression and therapy resistance.

K Deepak, Pritam Kumar Roy, Chandan Kanta Das, Budhaditya Mukherjee, Mahitosh Mandal.

Preserving a functional mitochondrial network is crucial for cellular well-being, considering the pivotal role of mitochondria in ensuring cellular survival, especially under stressful conditions. Mitophagy, the selective removal of damaged mitochondria through autophagy, plays a pivotal role in preserving cellular homeostasis by preventing the production of harmful reactive oxygen species from dysfunctional mitochondria. While the involvement of mitophagy in neurodegenerative diseases has been thoroughly investigated, it is becoming increasingly evident that mitophagy plays a significant role in cancer biology. Perturbations in mitophagy pathways lead to suboptimal mitochondrial quality control, catalyzing various aspects of carcinogenesis, including establishing metabolic plasticity, stemness, metabolic reconfiguration of cancer-associated fibroblasts, and immunomodulation. While mitophagy performs a delicate balancing act at the intersection of cell survival and cell death, mounting evidence indicates that, particularly in the context of stress responses induced by cancer therapy, it predominantly promotes cell survival. Here, we showcase an overview of the current understanding of the role of mitophagy in cancer biology and its potential as a target for cancer therapy. Gaining a more comprehensive insight into the interaction between cancer therapy and mitophagy has the potential to reveal novel targets and pathways, paving the way for enhanced treatment strategies for therapy-resistant tumors in the near future.

Keywords: Anticancer therapeutics; Drug resistance; Metabolic rewiring; Mitophagy; Pathway mechanism; Stemness maintenance

DOI: https://doi.org/10.1016/j.bbamcr.2024.119752