Review Interplay between Hypoxia Inducible Factor-1 and mitochondria in cardiac diseases 2024 Mialet-Perez and Belaidi

Highlights

• Interplay between HIF-1 mitochondria and ROS stand at the forefront of cardiac diseases
  
  
• Depending on the hypoxic stress, HIF-1 deciphers a paradoxical response that deserves to be deeply investigated
  
  
• The exploration of the “HIF-1 and mitochondria” crosstalk will open new avenues to understand cardiac diseases and propose new therapeutic strategies
  

Abstract

Ischemic heart diseases and cardiomyopathies are characterized by hypoxia, energy starvation and mitochondrial dysfunction. HIF-1 acts as a cellular oxygen sensor, tuning the balance of metabolic and oxidative stress pathways to provide ATP and sustain cell survival. Acting on mitochondria, HIF-1 regulates different processes such as energy substrate utilization, oxidative phosphorylation and mitochondrial dynamics. In turn, mitochondrial homeostasis modifications impact HIF-1 activity. This underlies that HIF-1 and mitochondria are tightly interconnected to maintain cell homeostasis.

Despite many evidences linking HIF-1 and mitochondria, the mechanistic insights are far from being understood, particularly in the context of cardiac diseases. Here, we explore the current understanding of how HIF-1, reactive oxygen species and cell metabolism are interconnected, with a specific focus on mitochondrial function and dynamics. We also discuss the divergent roles of HIF in acute and chronic cardiac diseases in order to highlight that HIF-1, mitochondria and oxidative stress interaction deserves to be deeply investigated. While the strategies aiming at stabilizing HIF-1 have provided beneficial effects in acute ischemic injury, some deleterious effects were observed during prolonged HIF-1 activation.

Thus, deciphering the link between HIF-1 and mitochondria will help to optimize HIF-1 modulation and provide new therapeutic perspectives for the treatment of cardiovascular pathologies.

Open access, https://www.sciencedirect.com/science/article/pii/S089158492400426X