Heat and mitochondrial bioenergetics

Abstract

Recurrent heat treatment (HT) is known to improve mitochondrial respiratory function and reduce mitochondrial reactive oxygen species (mROS) production over time. Counterintuitively, HT results in acute mitochondrial stress characterized by impaired mitochondrial respiratory function and increased mROS production. The combination of reduced adenosine triphosphate (ATP) synthesis and elevated mROS production leads to the activation of the adenosine monophosphate (AMP)-activated protein kinase, nuclear factor erythroid-2-related factor 2, proliferator-activated receptor gamma coactivator 1-alpha, and nuclear respiratory factor-1 signaling cascades, as well as the heat-shock response via activation of heat-shock factor 1. The coordinated transcriptional control of these proteins leads to the chronological induction of mitochondrial quality-control mechanisms, such as mitophagy and chaperone-mediated autophagy, and mitochondrial biogenesis/remodeling. Taken together, the acute stress imposed by HT leads to positive adaptations in mitochondrial health and function over time — making HT an attractive, nonpharmacologic treatment option for conditions characterized by mitochondrial dysfunction.