Peroxisome degradation in mammals

Abstract

SummaryThis review summarizes the historical aspects of the study of peroxisome degradation in mammalian cells. Peroxisomes have diverse metabolic roles in response to environmental changes and are degraded in a preferential manner, by comparison with cytosolic proteins. This review introduces three hypotheses on the degradation mechanisms: (a) the action of the peroxisomespecific Lon protease; (b) the membrane disruption effect of 15-lipoxygenase; and (c) autophagy that sequesters and degrades the organelles by lysosomal enzymes. Among these hypotheses, autophagy is now recognized as the most important mechanism for excess peroxisome degradation. One of the most striking characteristics of peroxisomes is that they are markedly proliferated in the liver by the administration of hypolipidemic drugs and industrial plasticizers. The effects of these substances were fully reversed after withdrawal of the substances, and most of the excess peroxisomes were selectively degraded and recovered to a normal number and size. Autophagic degradation of peroxisomes has been examined using this characteristic phenomenon. Excessive peroxisome degradation that occurs after cessation of hypolipidemic drugs has been extensively investigated biochemically and morphologically. The evidence shows that the degradation of excess peroxisomes and peroxisomal enzymes is inhibited by 3-methyladenine (3-MA), a specific inhibitor of autophagy. Furthermore, in liver-specific autophagy-deficient mice, rapid removal of peroxisomes was exclusively impaired, and degradation of peroxisomal enzymes was not detected. Thus, the significant contribution of autophagic machinery to peroxisomal degradation in mammals was confirmed. However, the important question of the mechanism for the selective recognition of peroxisomes by autophagosomes remains to be fully elucidated.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

“…Moreover, 2 additional degradation mechanisms have been suggested: the action of the peroxisome-specific LONP2/Lon (lon peptidase 2, peroxisomal) protease and the membrane disruption effect of 15lipoxygenase. 798 e. Chlorophagy Besides functioning as the primary energy suppliers for plants, chloroplasts represent a major source of fixed carbon and nitrogen to be remobilized from senescing leaves to storage organs and newly developing tissues. As such, the turnover of these organelles has long been considered to occur via an autophagytype mechanism.…”

PEX5 and Ubiquitin Dynamics on Mammalian Peroxisome Membranes

“…Since very little is known about the population structure of peroxisomes, we use a fixed peroxisomal radius in the middle of the range of reported peroxisomal sizes (0.1–0.8 in diameter [51]). We use peroxisomes, unless otherwise stated, which for purposes of computational efficiency is slightly smaller than the average number of reported for mammalian cells [52].…”

Transcriptional Regulation of 15-Lipoxygenase Expression by Histone H3 Lysine 4 Methylation/Demethylation

“…Deregulation of 15-LOX-1 expression is suggested to be involved in the pathogenesis of diverse malignancies, including prostate and colorectal cancer [4], , asthma [6], [7], atherosclerosis [8], orbital fibrosis [9] and nephritis [10]. Moreover, introduction of 15-LOX-1 into cells could result in oxidative stress and membrane degradation [11], [12]. Therefore, the expression and activity of the enzyme are strictly controlled.…”