Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health

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#humans #sirtuin-1 #organelle-biogenesis #peroxisome-proliferator-activated-receptor-gamma-coactivator-1-alpha #amp-activated-protein-kinases

Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health

Palabiyik et al., 2025 | Mol Biol Rep | Systematic Review

Citation

Palabiyik Ahmet Alperen, Palabiyik Esra. Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health. Mol Biol Rep. 2025-Feb-28;52(1):270. doi:10.1007/s11033-025-10368-8

Abstract

BACKGROUND: Mitochondrial biogenesis is essential for cellular energy balance and metabolic stability. Its dysregulation is linked to various metabolic and neurodegenerative diseases, making it a significant therapeutic target. Pharmacological approaches aimed at enhancing mitochondrial function have gained attention for their potential to restore cellular metabolism. OBJECTIVES: This review examines recent advancements in pharmacological strategies targeting mitochondrial biogenesis, focusing on the roles of PGC-1α, AMPK, and SIRT1, alongside novel therapeutic agents and drug delivery systems. METHODS: A systematic review of studies published between 2018 and 2023 was conducted using databases such as PubMed, Web of Science, and Elsevier. Keywords related to mitochondrial biogenesis and pharmacological modulation were used to identify relevant literature. RESULTS: Various pharmacological agents, including resveratrol, curcumin, and metformin, activate mitochondrial biogenesis through different pathways. SIRT1 activators and AMPK agonists have shown promise in improving mitochondrial function. Advances in mitochondria-targeted drug delivery systems enhance therapeutic efficacy, yet challenges remain in clinical translation due to the complexity of mitochondrial regulation. CONCLUSION: Pharmacological modulation of mitochondrial biogenesis holds therapeutic potential for metabolic and neurodegenerative diseases. While preclinical studies are promising, further research is needed to optimize drug efficacy, delivery methods, and personalized treatment strategies.

Key Findings

Various pharmacological agents, including resveratrol, curcumin, and metformin, activate mitochondrial biogenesis through different pathways. SIRT1 activators and AMPK agonists have shown promise in improving mitochondrial function. Advances in mitochondria-targeted drug delivery systems enhance therapeutic efficacy, yet challenges remain in clinical translation due to the complexity of mitochondrial regulation.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Sirtuin 1
  • Organelle Biogenesis
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • AMP-Activated Protein Kinases
  • Mitochondria
  • Animals
  • Neurodegenerative Diseases
  • Resveratrol
  • Metformin
  • Energy Metabolism
  • Drug Delivery Systems
  • Curcumin

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: curcumin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09