Peptide YY fragment PYY1-36 disrupts mitochondrial biogenesis via RBM43-dependent PGC-1α translation inhibition DOI Creative Commons
Benkun Liu,

Fucheng Zhou,

Bao‐Sen Shi

et al.

Investigational New Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: May 22, 2025

Mitochondrial dysfunction is a key driver of cancer progression, with therapies increasingly targeting metabolic weaknesses. Peptide YY (PYY), gastrointestinal hormone, regulates cellular activity, but its influence on mitochondrial health in lung remains poorly understood. We explored how PYY1-36, bioactive fragment PYY, affects stability NCI-H1581 cells. Using dose-response experiments, we measured oxidative stress by tracking lactate dehydrogenase (LDH) release, ROS levels, and DNA damage (8-OHdG). Energy production was evaluated through ATP oxygen consumption rates (OCR), Complex I activity. also analyzed biogenesis markers (NRF1, TFAM, PGC-1α) the RNA-binding protein RBM43 via qPCR immunoblotting. Dose-dependent tests showed that PYY1-36 triggers damage, marked higher LDH release spikes. These changes aligned sharp drops disrupted respiratory function. Notably, reduced mass biogenesis, supported weaker MitoTracker Red signals lower mtDNA/nDNA ratios. Key regulators NRF1 TFAM were strongly suppressed, pointing to widespread failure. Intriguingly, blocked PGC-1α synthesis without altering mRNA suggesting post-transcriptional control mechanism. boosted levels. Knocking down reversed PYY1-36's effects health. Our findings reveal as central player PYY1-36-induced suppression translation. Targeting could unlock new strategies tackle chaos cancer.

Language: Английский

Peptide YY fragment PYY1-36 disrupts mitochondrial biogenesis via RBM43-dependent PGC-1α translation inhibition DOI Creative Commons
Benkun Liu,

Fucheng Zhou,

Bao‐Sen Shi

et al.

Investigational New Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: May 22, 2025

Mitochondrial dysfunction is a key driver of cancer progression, with therapies increasingly targeting metabolic weaknesses. Peptide YY (PYY), gastrointestinal hormone, regulates cellular activity, but its influence on mitochondrial health in lung remains poorly understood. We explored how PYY1-36, bioactive fragment PYY, affects stability NCI-H1581 cells. Using dose-response experiments, we measured oxidative stress by tracking lactate dehydrogenase (LDH) release, ROS levels, and DNA damage (8-OHdG). Energy production was evaluated through ATP oxygen consumption rates (OCR), Complex I activity. also analyzed biogenesis markers (NRF1, TFAM, PGC-1α) the RNA-binding protein RBM43 via qPCR immunoblotting. Dose-dependent tests showed that PYY1-36 triggers damage, marked higher LDH release spikes. These changes aligned sharp drops disrupted respiratory function. Notably, reduced mass biogenesis, supported weaker MitoTracker Red signals lower mtDNA/nDNA ratios. Key regulators NRF1 TFAM were strongly suppressed, pointing to widespread failure. Intriguingly, blocked PGC-1α synthesis without altering mRNA suggesting post-transcriptional control mechanism. boosted levels. Knocking down reversed PYY1-36's effects health. Our findings reveal as central player PYY1-36-induced suppression translation. Targeting could unlock new strategies tackle chaos cancer.

Language: Английский

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