Cellular and Intercellular Homeostasis in Adipose Tissue with Mitochondria-Specific Stress

Paracrine interactions are imperative for the maintenance of adipose tissue intercellular homeostasis, and intracellular organelle dysfunction results in local and systemic alterations in metabolic homeostasis. It is currently accepted that mitochondrial proteotoxic stress activates the mitochondrial unfolded protein response (UPR(mt)) in vitro and in vivo. The induction of mitochondrial chaperones and proteases during the UPR(mt) is a key cell-autonomous mechanism of mitochondrial quality control. The UPR(mt) also affects systemic metabolism through the secretion of cell non-autonomous peptides and cytokines (hereafter, metabokines). Mitochondrial function in adipose tissue plays a pivotal role in whole-body metabolism and human diseases. Despite continuing interest in the role of the UPR(mt) and quality control pathways of mitochondria in energy metabolism, studies on the roles of the UPR(mt) and metabokines in white adipose tissue are relatively sparse. Here, we describe the role of the UPR(mt) in adipose tissue, including adipocytes and resident macrophages, and the interactive roles of cell non-autonomous metabokines, particularly growth differentiation factor 15, in local adipose cellular homeostasis and systemic energy metabolism.