Environmental and behavioral regulation of HIF-mitochondria crosstalk, 2023, Johannes Burtscher et al

Highlights

• Hypoxia inducible factors – mitochondria crosstalk underlies adaptations to hypoxia.
  
  
• Controlled induction of hypoxia responses yields potent health benefits.
  
  
• Environmental and behavioral conditions modulate adaptations to hypoxia.
  
  
• Understanding the determinants of adaptation efficiency/safety are key for clinical applications.

Abstract
Reduced oxygen availability (hypoxia) can lead to cell and organ damage. Therefore, aerobic species depend on efficient mechanisms to counteract detrimental consequences of hypoxia. Hypoxia inducible factors (HIFs) and mitochondria are integral components of the cellular response to hypoxia and coordinate both distinct and highly intertwined adaptations. This leads to reduced dependence on oxygen, improved oxygen supply, maintained energy provision by metabolic remodeling and tapping into alternative pathways and increased resilience to hypoxic injuries.

On one hand, many pathologies are associated with hypoxia and hypoxia can drive disease progression, for example in many cancer and neurological diseases. But on the other hand, controlled induction of hypoxia responses via HIFs and mitochondria can elicit profound health benefits and increase resilience.

To tackle pathological hypoxia conditions or to apply health-promoting hypoxia exposures efficiently, cellular and systemic responses to hypoxia need to be well understood. Here we first summarize the well-established link between HIFs and mitochondria in orchestrating hypoxia-induced adaptations and then outline major environmental and behavioral modulators of their interaction that remain poorly understood.

https://www.sciencedirect.com/science/article/pii/S0891584923005026?via=ihub