Abstract
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells. We first outline how peroxisomal and mitochondrial abundance are controlled by common sets of cis- and trans-acting factors. Next, we discuss how peroxisomes and mitochondria may communicate with each other at the molecular level. In addition, we reflect on how these organelles cooperate in various metabolic and signaling pathways. Finally, we address why peroxisomes and mitochondria have to maintain a healthy relationship and why defects in one organelle may cause dysfunction in the other. Gaining a better insight into these issues is pivotal to understanding how these organelles function in their environment, both in health and disease.
Highlights
Eukaryotic cells are endowed with a diverse array of structurally and functionally discrete membrane-enclosed organelles
These findings are in line with a study in Saccharomyces cerevisiae showing that respiratory deficiency, but not inhibition of mitochondrial adenosine triphosphate (ATP) synthesis per se, dramatically induces peroxisome biogenesis and function through activation of retrograde signaling pathways [130]
Given that peroxisomes and mitochondria play a central role in cellular lipid metabolism [92], and that lipids play multiple roles in cellular signaling, bioenergetics, and membrane structure and function [134], changes in peroxisomal or mitochondrial lipid metabolism would be expected to influence the function of the other organelle
Summary
Eukaryotic cells are endowed with a diverse array of structurally and functionally discrete membrane-enclosed organelles Such compartmentalization provides several distinct benefits, including (i) the creation of different local environments that facilitate specific metabolic functions; (ii) the sequestering of reaction intermediates and potentially toxic metabolites; and (iii) the ability to perform specific functions without interfering with other cellular processes [1]. Mitochondria are dynamic organelles that continuously adapt their number, morphology, and function to prevailing environmental conditions [12]. In mammals, these organelles play a central role in many metabolic processes including–among others–adenosine triphosphate (ATP) generation, β-oxidation of fatty acids, ketone body production, and iron-sulfur cluster synthesis [13,14]. We provide an overview of what is currently known about the interplay between peroxisomes and mitochondria under various disease conditions (see Section 6)
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