Abstract
Mitochondria regulate several key processes that are fundamental to cellular health, including energy production, calcium buffering, metabolism of amino acids, nucleotides, and lipids, and cell survival. To maintain organelle health under conditions of mitochondrial dysfunction, cells rely on sophisticated quality control mechanisms, which aim to either restore organelle homeostasis or remove and replace severely damaged mitochondria. In this chapter, we discuss the signaling events involved in the activation and regulation of the mitochondrial unfolded protein response (UPRmt) as a first line of defense mechanism against stress. We also examine the functional crosstalk between UPRmt and other homeostatic signaling cascades, including the integrated stress response and mitophagy, and their synergy to maintain mitochondrial and cellular health.