Polyphenols in mtDNA Repair, Mitochondrial Biogenesis, and Mitophagy: An Integrative Review

Victoria-Montesinos, D., Barcina-Pérez, P., García-Muñoz, A.M. (2026). Polyphenols in mtDNA Repair, Mitochondrial Biogenesis, and Mitophagy: An Integrative Review. BIOCELL, 50(6), 2. doi:10.32604/biocell.2026.077286 

 Mitochondrial dysfunction is a central hallmark of metabolic, hepatic, cardiovascular, and neurodegenerative diseases. Dietary polyphenols modulate mitochondrial pathways, but their integrated effects remain poorly appreciated. This narrative review synthesizes preclinical and clinical evidence on four polyphenols (resveratrol, epigallocatechin-3-gallate, quercetin, and oleuropein) and examines their mechanisms in mitochondrial biogenesis, mtDNA protection, and mitophagy. Experimental studies indicate that these compounds activate conserved adaptive pathways, including sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), AMP-activated protein kinase (AMPK), and PTEN-induced kinase 1 (PINK1) with Parkin, therapy enhancing mitochondrial biogenesis, reducing oxidative stress, and promoting selective removal of damaged mitochondria

Genetic modifiers of Friedreich's ataxia pathophysiology in Drosophila melanogaster - A systematic review and meta-analysis

Ravi Kant Yadav, Vishnu Swarup, Anami Ahuja, Dipesh Talukdar, Divyani Garg, Muraleedhar Aski, Achal Kumar Srivastava, Prachi Yadav, Genetic modifiers of Friedreich's ataxia pathophysiology in Drosophila melanogaster - A systematic review and meta-analysis, Free Radical Biology and Medicine, Volume 254, 2026, Pages 196-210,, ISSN 0891-5849, doi:10.1016/j.freeradbiomed.2026.06.031. 

 Ferritins overexpression, Miro inhibition, and catalase overexpression, converging pathways iron homeostasis, mitochondrial dynamics and oxidative stress management, were found to be the top ranked modifiers for their beneficial effects on FRDA pathophysiology and were suggested for further studies as therapeutic targets.

Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model

Lees, J.G., Zhang, H., Jiao, L. et al. Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model. Cell Death Dis (2026). doi:10.1038/s41419-026-09030-3

 RNA sequencing revealed a distinct transcriptional profile associated with frataxin deficiency. MEG3 and PCDHGA10 were consistently dysregulated across all three FRDA-iPSC lines and may represent early molecular markers of FRDA cardiomyopathy. Functional interrogation of these candidates demonstrated that targeted silencing of MEG3 or PCDHGA10 in FRDA cardiomyocytes significantly reduced disease‑associated cell death without affecting FXN expression. Notably, PCDHGA10 silencing also normalized elevated mitochondrial reactive oxygen species, whereas MEG3 silencing did not, highlighting gene‑specific contributions to FRDA cardiomyocyte survival. Collectively, these findings identify MEG3 and PCDHGA10 as functionally relevant regulators of FRDA cardiomyocyte pathology.

Dysregulation of sphingolipid-metabolizing enzymes in Friedreich’s ataxia: In vitro and in vivo insights into therapeutic targeting

Ramchunder Z, Kalef-Ezra E, Suleman S ..., Dysregulation of sphingolipid-metabolizing enzymes in Friedreich’s ataxia: In vitro and in vivo insights into therapeutic targeting, iScience, 2026; 29. DOI: 10.1016/j.isci.2026.116479 

 Sphingolipids are increasingly recognized for their roles in neurodegeneration with emerging evidence indicating their dysregulation in FRDA. Here, we investigate whether sphingolipid-metabolizing enzymes are similarly affected and assess the therapeutic potential of targeting them. Our findings demonstrate that these enzymes are dysregulated across multiple FRDA models. Importantly, their modulation in vitro and in vivo significantly reduces mitochondrial dysfunction, enhances frataxin expression, and improves key pathological features of the disease, highlighting sphingolipid metabolism as a promising therapeutic target for FRDA.