Peroxisomes as cellular adaptors to metabolic and environmental stress

He, Anbang; Dean, John M.; Lodhi, Irfan J.

doi:10.1016/j.tcb.2021.02.005

Cited by 72 publications

(47 citation statements)

References 93 publications

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“…Peroxisomes, abundant in cells that are involved in lipid and xenobiotics metabolism, play a major role in the breakdown of long-chain fatty acids, thereby complementing mitochondrial fatty-acid oxidation [25]. In our study we demonstrated that the age is associated with the decrease in relative number of peroxisomes in hepatocytes, and FN administration increases the relative number of peroxisomes only in hepatocytes of old rats.…”

Section: Discussionsupporting

confidence: 58%

Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

Zubrzycki

Wrońska

Zauszkiewicz-Pawlak

et al. 2021

Folia Histochem Cytobiol.

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Introduction. Fenofibrate (FN) is a hypolipemic drug used for the treatment of mixed dyslipidemia. Since in our previous study FN administration to young and old rats adversely affected the serum activity of liver marker enzymes, we decided to examine the effects of FN on liver ultrastructure of young and old animals.Material and methods. Young and old rats were fed standard rodent chow supplemented with 0.1% FN for 30 days. Liver samples obtained from animals under full anesthesia were processed by routine methods to obtain ultrathin and histological sections for the examination by light microscopy (LM) and transmission electron microscopy (TEM). Furthermore, liver lysates were analyzed by Western blotting for the expression of the autophagy-related proteins LC3A/B and beclin 1.Results. The ultrastructure of hepatocytes in both age groups was well-preserved, with the presence of abundant mitochondria, numerous peroxisomes and lysosomes, glycogen stored in the form of rosettes, and occasionally autolysosomes. However, hepatocytes of old control rats contained less mitochondria and peroxisomes, and more lipid droplets than cells of young animals. The effects of FN on liver ultrastructure were age-depended. FN increased the relative number of mitochondria and peroxisomes in the hepatocytes of old, and did not affect their number in young rats. Moreover, FN decreased and increased the relative number of lipid droplets in the hepatocytes of old and young rats, respectively. At the LM level, Oil Red O staining revealed smaller and larger lipid droplets within hepatocytes and non-parenchymal liver cells. In the livers of young and old rats lipid droplets were distributed mainly in the periportal zones of hepatic lobules. Morphometric analysis confirmed that livers of control old rats contained more lipid-stainable areas than those of young ones; however, no effect of FN was observed either in young or old rats. Despite larger size of autolysosomes and autophagic vacuoles in hepatocytes of old rats, the expression of autophagy-related proteins did not differ in the livers of control and fenofibrate-treated young and old animals. Conclusions.The results of our study suggest that fenofibrate, apart from its hypolipemic action, may have beneficial effect on the energy metabolism in the liver of old individuals by increasing the number of mitochondria and peroxisomes in hepatocytes.

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Section: Discussionsupporting

confidence: 58%

Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

Zubrzycki

Wrońska

Zauszkiewicz-Pawlak

et al. 2021

Folia Histochem Cytobiol.

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“…Since peroxisomal lipid metabolism requires cooperation and interaction with mitochondria, ER and LDs, peroxisomal ABC transporters, through their interactome, could therefore actively participate in this intracellular metabolic network. Peroxisome-organelle interactions have physiological relevance [ 166 , 173 ], and peroxisomes are increasingly considered important intracellular signaling platforms that modulate physiological processes such as inflammation, innate immunity and cell fate decision [ 12 , 174 , 175 ]. Peroxisomal ABC transporters would play an essential part in this emerging role of peroxisomes in signaling pathways such as calcium signaling as highlighted in this review.…”

Section: Protein Interactions and Unexpected Rolesmentioning

confidence: 99%

Peroxisomal ABC Transporters: An Update

Tawbeh

Gondcaille

Trompier

et al. 2021

IJMS

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ATP-binding cassette (ABC) transporters constitute one of the largest superfamilies of conserved proteins from bacteria to mammals. In humans, three members of this family are expressed in the peroxisomal membrane and belong to the subfamily D: ABCD1 (ALDP), ABCD2 (ALDRP), and ABCD3 (PMP70). These half-transporters must dimerize to form a functional transporter, but they are thought to exist primarily as tetramers. They possess overlapping but specific substrate specificity, allowing the transport of various lipids into the peroxisomal matrix. The defects of ABCD1 and ABCD3 are responsible for two genetic disorders called X-linked adrenoleukodystrophy and congenital bile acid synthesis defect 5, respectively. In addition to their role in peroxisome metabolism, it has recently been proposed that peroxisomal ABC transporters participate in cell signaling and cell control, particularly in cancer. This review presents an overview of the knowledge on the structure, function, and mechanisms involving these proteins and their link to pathologies. We summarize the different in vitro and in vivo models existing across the species to study peroxisomal ABC transporters and the consequences of their defects. Finally, an overview of the known and possible interactome involving these proteins, which reveal putative and unexpected new functions, is shown and discussed.

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“…Currently, it is widely accepted that peroxisomes can act as H2O2 signaling platforms, thereby conveying metabolic information into redox signaling events [Fransen and Lismont, 2019;He et al, 2021]. However, little is known about the molecular targets of peroxisomal H2O2 and, to address this gap, we designed an efficient and unique sulfenome mining approach to capture and identify such targets in a dynamic manner.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome-derived hydrogen peroxide can modulate the sulfenylation profiles of key redox signaling proteins

Lismont

Revenco

et al. 2021

Preprint

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Ever since the first characterization of peroxisomes, a central theme has been their involvement in cellular hydrogen peroxide (H2O2) metabolism. While the reputation of H2O2 drastically changed from an exclusively toxic molecule to a signaling messenger, the regulatory role of peroxisomes in these signaling events is still largely underappreciated. This is mainly because the number of known protein targets of peroxisome-derived H2O2 is rather limited and testing of specific targets is predominantly based on knowledge previously gathered in related fields of research. To gain a broader and more systematic insight into the role of peroxisomes in redox signaling, an unbiased approach is urgently needed. To accomplish this goal, we have combined a previously developed cell system in which peroxisomal H2O2 production can be modulated with a yeast AP-1-like-based sulfenome mining strategy to inventory protein thiol targets of peroxisome-derived H2O2 in different subcellular compartments. Using this unbiased approach, we were able to identify specific and common targets of peroxisome-derived and exogenous H2O2 in peroxisomes, the cytosol, and mitochondria. We also observed that the sulfenylation kinetics profiles of key targets belonging to different protein families can vary considerably. In addition, we obtained compelling but indirect evidence that peroxisome-derived H2O2 may oxidize at least some of its targets through a redox relay mechanism. In conclusion, given that sulfenic acids function as key intermediates in H2O2 signaling, the findings presented in this study provide initial but critical insight into how peroxisomes may be integrated in the cellular H2O2 signaling network.

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Peroxisomes as cellular adaptors to metabolic and environmental stress

Cited by 72 publications

References 93 publications

Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

Peroxisomal ABC Transporters: An Update

Peroxisome-derived hydrogen peroxide can modulate the sulfenylation profiles of key redox signaling proteins

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