The emerging role of immune dysfunction in mitochondrial diseases as a paradigm for understanding immunometabolism

Abstract

Immunometabolism aims to define the role of intermediary metabolism in immune cell function, with bioenergetics and the mitochondria recently taking center stage. To date, the medical literature on mitochondria and immune function extols the virtues of mouse models in exploring this biologic intersection. While the laboratory mouse has become a standard for studying mammalian biology, this model comprises part of a comprehensive approach. Humans, with their broad array of inherited phenotypes, serve as a starting point for studying immunometabolism; specifically, patients with mitochondrial disease. Using this top-down approach, the mouse as a model organism facilitates further exploration of the consequences of mutations involved in mitochondrial maintenance and function. In this review, we will discuss the emerging phenotype of immune dysfunction in mitochondrial disease as a model for understanding the role of the mitochondria in immune function in available mouse models.

Keywords: Bioenergetics; Immunity; Mitochondria; Mouse models; Oxidative phosphorylation.

Figure. Human mitochondrial morbidity map as a guide for identifying mitochondrial disease patients that may have defects in innate or adaptive immune responses

Cartoon provides a list of known mtDNA or nDNA-encoded mitochondrial disease-associated genes, and in which key mitochondrial function that gene product is known to play a role: (A) mitochondrial calcium transport, mitochondrial membrane (B) fission and (C) fusion, (D) mtDNA replication and stability, or (E) the respiratory chain. Genes listed were compiled from MitoMap [169].