Peroxisomes: role in cellular ageing and age related disorders

Abstract

Peroxisomes are dynamic organelles essential for optimum functioning of a eukaryotic cell. Biogenesis of these organelles and the diverse functions performed by them have been extensively studied in the past decade. Their ability to perform functions depending on the cell type and growth conditions is unique and remarkable. Oxidation of fatty acids and reactive oxygen species metabolism are the two most important functions of these ubiquitous organelles. They are often referred to as both source and sink of reactive oxygen species in a cell. Recent research connects peroxisome dysfunction to fatal oxidative damage associated with ageing-related diseases/disorders. It is now widely accepted that mitochondria and peroxisomes are required to maintain oxidative balance in a cell. However, our understanding on the inter-dependence of these organelles to maintain cellular homeostasis of reactive oxygen species is still in its infancy. Herein, we summarize findings that highlight the role of peroxisomes in cellular reactive oxygen species metabolism, ageing and age-related disorders.

The peroxisome: an update on mysteries 2.0

“…Last but not least, they are involved in fundamental vital processes such as the detoxification of dangerous oxygen/nitrogen species (Fransen et al 2012 ), are signalling platforms (Mast et al 2015 ), with critical roles for innate immunity (Dixit et al 2010 ) as well as development and differentiation (Titorenko and Rachubinski 2004 ), and intimately communicate with other organelles (Schrader et al 2013 ; Shai et al 2016 ). Dysfunctions or even lack of peroxisomes not only underlie the well-known peroxisomal disorders, but also contribute to physio- as well as patho-physiological processes such as ageing and related diseases (Deori et al 2018 ) or cancer (see “ Peroxisomes and cancer: a mysterious connection ”).…”

“…In view of their diverse metabolic functions, in particular their role both as source and sink of ROS in a cell, peroxisomes are a predestined hub in cellular ageing. Indeed, a plethora of studies employing cell lines of diverse origin, animals, and yeast cultures report on profound alterations in the biogenesis and proliferation of the organelle, in the rate of expression as well as location of peroxisomal enzymes engaged in ROS metabolism (catalase), and last but not least in the interaction with other cell organelles, particularly mitochondria (Deori et al 2018 and ref. therein).…”

HSD17B4, ACAA1, and PXMP4 in Peroxisome Pathway Are Down-Regulated and Have Clinical Significance in Non-small Cell Lung Cancer

“…Metabolic reprogramming is one of the core traits of the cancer cells, due to the multiple alterations during the multi-step process of tumorigenesis (Soga, 2013;El Hassouni et al, 2019). In recent years, with the deepening understanding of the important functions of the peroxisomes, more and more attention were paid to the peroxisomes research (Tanner et al, 2013;El Hassouni et al, 2019) and they were demonstrated to be implicated in innate immunity (Ferreira et al, 2019), signal transduction (Schrul and Schliebs, 2018), aging (Deori et al, 2018), and cancer (Dahabieh et al, 2018).…”

A genome-wide screen identifies genes that suppress the accumulation of spontaneous mutations in young and aged yeast cells

“…Given the evolutionary conservation of this and many other peroxisome biogenesis factors, it would be interesting to test the contribution of peroxisomes in genome maintenance during mammalian cell aging and cancer development. Indeed, several studies have reported the absence of peroxisomes in cancer cells [89–91], suggesting a possible link between peroxisome biogenesis defects and tumorigenesis [92].…”