Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum
Open accessAbstract
Peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways which include: (1.) etherphospholipid biosynthesis; (2.) fatty acid beta-oxidation; (3.) bile acid synthesis; (4.) docosahexaenoic acid (DHA) synthesis; (5.) fatty acid alpha-oxidation; (6.) glyoxylate metabolism; (7.) amino acid degradation, and (8.) ROS/RNS metabolism. The importance of peroxisomes for human health and development is exemplified by the existence of a large number of inborn errors of peroxisome metabolism in which there is an impairment in one or more of the metabolic functions of peroxisomes. Although the clinical signs and symptoms of affected patients differ depending upon the enzyme which is deficient and the extent of the deficiency, the disorders involved are usually (very) severe diseases with neurological dysfunction and early death in many of them. With respect to the role of peroxisomes in metabolism it is clear that peroxisomes are dependent on the functional interplay with other subcellular organelles to sustain their role in metabolism. Indeed, whereas mitochondria can oxidize fatty acids all the way to CO2 and H2O, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal beta-oxidation need to be shuttled to mitochondria for full oxidation to CO2 and H2O. Furthermore, NADH is generated during beta-oxidation in peroxisomes and beta-oxidation can only continue if peroxisomes are equipped with a mechanism to reoxidize NADH back to NAD(+), which is now known to be mediated by specific NAD(H)-redox shuttles. In this paper we describe the current state of knowledge about the functional interplay between peroxisomes and other subcellular compartments notably the mitochondria and endoplasmic reticulum for each of the metabolic pathways in which peroxisomes are involved.
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All of these metabolites must be transferred into mitochondria for full β-oxidation into CO2 and H2O because peroxisomes lack a Krebs' cycle.
“All of these metabolites must be transferred into mitochondria for full β-oxidation into CO2 and H2O because peroxisomes lack a Krebs’ cycle [162].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [162]
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“Peroxisomes are involved in redox balance, lipid metabolism and bile acid synthesis [282, 283].”
BackgroundCrosstalk Between Mammalian Autophagy and the Ubiquitin-Proteasome System
Kocatürk, N. M., & Gözüaçık, D. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00128 · Cited by 415 · see citing works
Dietary Restriction and AMPK Increase Lifespan via Mitochondrial Network and Peroxisome Remodeling
Weir, H. J., Yao, P., Huynh, F. K., Escoubas, C. C., Goncalves, R. L., Burkewitz, K., Laboy, R., Hirschey, M. D., & Mair, W. B. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.024 · Cited by 372 · see citing works
“Functional interplay exists between mitochondria and peroxisomes in the regulation of FAO, and oxidation of very long- and long-chain fatty acids takes place in peroxisomes (Wanders et al., 2016).”
The Peroxisome-Mitochondria Connection: How and Why?
Fransen, M., Lismont, C., & Walton, P. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061126 · Cited by 351 · see citing works
“Peroxisomes and mitochondria contain distinct sets of enzymes for each β-oxidation reaction step, and as such it is no surprise that both organelles have largely different substrate specificities [26,88].”
BackgroundInfluentialL-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine
McCann, M. R., la Rosa, M. V. G. D., Rosania, G. R., & Stringer, K. A. (2021) · Metabolites · doi:10.3390/metabo11010051 · Cited by 328 · see citing works
“Peroxisomes utilize the carnitine shuttle to transport the end-products (acetyl-CoA, propionyl-CoA, and medium-chain acyl-CoA) into the mitochondria for complete oxidation via the TCA cycle [7,37].”
BackgroundUbiquitin-mediated regulation of autophagy
Chen, R., Chen, Y.-H., & Huang, T.-Y. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0569-y · Cited by 320 · see citing works
“Peroxisomes are ubiquitous organelles involving in modulation of metabolic responses and redox regulation [84].”
BackgroundThe peroxisome: an update on mysteries 2.0
Islinger, M., Völkl, A., Fahimi, H. D., & Schrader, M. (2018) · Histochemistry and Cell Biology · doi:10.1007/s00418-018-1722-5 · Cited by 287 · see citing works
“Peroxisomes are not isolated entities in the cell but communicate and share signals, metabolites and proteins with other compartments including the ER, mitochondria, lipid droplets and lysosomes (for recent reviews see Schrader et al. 2015; Wanders et al. 2016; Shai et al. 2016; Yoboue et al. 2018; Castro et al. 2018)…”
BackgroundCompartmentalised acyl-CoA metabolism and roles in chromatin regulation
Trefely, S., Lovell, C. D., Snyder, N. W., & Wellen, K. E. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.005 · Cited by 272 · see citing works
Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα
Tahri-Joutey, M., Andreoletti, P., Surapureddi, S., Nasser, B., Cherkaoui‐Malki, M., & Latruffe, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168969 · Cited by 258 · see citing works
Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis
Das, K. P., Wood, C. R., Lin, M. T., Starkov, A. A., Lau, C. S., Wallace, K. B., Corton, J. C., & Abbott, B. D. (2017) · Toxicology · doi:10.1016/j.tox.2016.12.007 · Cited by 260 · see citing works
“Peroxisomes and mitochondria share a critical interplay in fatty acid (Schrader et al., 2015; Wanders et al., 2016).”
BackgroundYoboue, E. D., Sitia, R., & Simmen, T. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0033-4 · Cited by 238 · see citing works
The physiological functions of human peroxisomes
Wanders, R. J. A., Baes, M., Ribeiro, D., Ferdinandusse, S., & Waterham, H. R. (2023) · Physiological Reviews · doi:10.1152/physrev.00051.2021 · Cited by 228 · see citing works
Self-citationExosomes in inflammation and role as biomarkers
Console, L., Scalise, M., & Indiveri, C. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.11.009 · Cited by 216 · see citing works
Chai, X., Han, H., Sedgwick, A. C., Li, N., Zang, Y., James, T. D., Zhang, J., Hu, X., Yu, Y., Li, Y., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.0c05379 · Cited by 206 · see citing works
Mechanisms Orchestrating Mitochondrial Dynamics for Energy Homeostasis
Yu, S. B., & Pekkurnaz, G. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.07.027 · Cited by 182 · see citing works
“The molecular mechanisms regulating the physical interconnection of these two organelles still need to be elucidated [104,105].”
BackgroundPlant peroxisomes: A nitro-oxidative cocktail
Corpas, F. J., Barroso, J. B., Palma, J. M., & Rodríguez-Ruiz, M. (2017) · Redox Biology · doi:10.1016/j.redox.2016.12.033 · Cited by 178 · see citing works
Microglia and lipids: how metabolism controls brain innate immunity
Chausse, B., Kakimoto, P. A., & Kann, O. (2021) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2020.08.001 · Cited by 181 · see citing works
ROS signaling in innate immunity via oxidative protein modifications
Manoharan, R. R., Prasad, A., Pospı́šil, P., & Kzhyshkowska, J. G. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1359600 · Cited by 163 · see citing works
Ruiz, M., Labarthe, F., Fortier, A., Bouchard, B., Legault, J. T., Bolduc, V., Rigal, O., Chen, J., Ducharme, A., Crawford, P. A., et al. (2017) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00820.2016 · Cited by 155 · see citing works
“—Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FAs), which remain to be better understood in humans.”
BackgroundResultInfluentialOxidative stress, antioxidants and intestinal calcium absorption
de Barboza, G. D., Guizzardi, S., Moine, L., & de Talamoni, N. T. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i16.2841 · Cited by 149 · see citing works
Organelle interplay-peroxisome interactions in health and disease.
Schrader, M., Kamoshita, M., & Islinger, M. (2020) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12083 · Cited by 149 · see citing works
Peroxisomes: Versatile organelles with diverse roles in plants
Pan, R., Liu, J., Wang, S., & Hu, J. (2020) · New Phytologist · doi:10.1111/nph.16134 · Cited by 145 · see citing works
Effect of Maternal Obesity on Placental Lipid Metabolism
Calabuig-Navarro, V., Haghiac, M., Minium, J., Glazebrook, P. A., Ranasinghe, G. C., Hoppel, C. L., Mouzon, S. H., Catalano, P., & O’Tierney-Ginn, P. (2017) · Endocrinology · doi:10.1210/en.2017-00152 · Cited by 144 · see citing works
“First Published Online 23 May 2017 Abbreviations: AC, acylcarnitine; ACC, acetyl-CoA carboxylase; BMI, body mass index; BSA, bovine serum albumin; CACT, carnitine/acylcarnitine translocase; CI, confidence interval; COT, peroxisomal carnitineO-octanoyltransferase; CPT, carnitine palmitoyltransferase; CytB, cytochrome B…”
BackgroundInfluentialFunctional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides
Coradetti, S. T., Pinel, D., Geiselman, G. M., Ito, M., Mondo, S. J., Reilly, M. C., Cheng, Y.-F., Bauer, Š., Grigoriev, I. V., Gladden, J. M., et al. (2018) · eLife · doi:10.7554/elife.32110 · Cited by 134 · see citing works
Peroxisomes in Immune Response and Inflammation
Cara, F. D., Andreoletti, P., Trompier, D., Véjux, A., Bülow, M. H., Sellin, J., Lizard, G., Cherkaoui‐Malki, M., & Savary, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163877 · Cited by 127 · see citing works
Takeshita, Y., Honda, M., Harada, K., Kita, Y., Takata, N., Tsujiguchi, H., Tanaka, T., Goto, H., Nakano, Y., Iida, N., et al. (2022) · Diabetes Care · doi:10.2337/dc21-2049 · Cited by 130 · see citing works
“Rescuing zone 3 hepatocytes could enhance various redox signalings, such as glutathione pathways, that remove reactive oxygen species induced by oxidative lipid (50).”
BackgroundPeroxisome Metabolism in Cancer
Kim, J. (2020) · Cells · doi:10.3390/cells9071692 · Cited by 123 · see citing works
“Peroxisome formation and peroxisome metabolism are linked to the functions of other organelles, such as the ER and mitochondria [21,120].”
BackgroundInfluentialXiang, F., Zhang, Z., Xie, J., Xiong, S., Chen, Y., Liao, D., Xia, B., & Lin, L. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06341-5 · Cited by 100 · see citing works
Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation
Misheva, M., Kotzamanis, K., Davies, L. C., Tyrrell, V. J., Rodrigues, P. D. S., Benavides, G. A., Hinz, C., Murphy, R. C., Kennedy, P. D., Taylor, P. R., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27766-8 · Cited by 98 · see citing works
“It has been proposed that truncated unsaturated FA metabolites may need to transfer to mitochondria for complete metabolism 82 .”
BackgroundMapping Proteome-wide Targets of Glyphosate in Mice
Ford, B., Bateman, L. A., Gutierrez-Palominos, L., Park, R., & Nomura, D. K. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2016.12.013 · Cited by 96 · see citing works
Peroxisomes and cancer: The role of a metabolic specialist in a disease of aberrant metabolism
Dahabieh, M. S., Pietro, E. D., Jangal, M., Gonçalves, C., Witcher, M., Braverman, N., & Rincon, S. V. D. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.07.004 · Cited by 96 · see citing works
Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss
Collin, G. B., Gogna, N., Chang, B., Damkham, N., Pinkney, J., Hyde, L. F., Stone, L. V., Naggert, J. Κ., Nishina, P. M., & Krebs, M. P. (2020) · Cells · doi:10.3390/cells9040931 · Cited by 94 · see citing works
“Peroxisomes are subcellular organelles with various catabolic and anabolic functions such as catabolism of long chain fatty acids and biosynthesis of DHA and bile acids [280].”
BackgroundMitochondrial and metabolic alterations in cancer cells
Gregorio, J. D., Petricca, S., Iorio, R., Toniato, E., & Flati, V. (2022) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2022.151225 · Cited by 93 · see citing works
Cho, I., Adelmant, G., Lim, Y., Marto, J. A., Cho, G., & Golden, J. A. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.795286 · Cited by 89 · see citing works
“Peroxisomes and mitochondria functionally and physically interact to maintain lipid homeostasis through -oxidation of fatty acids and scavenging reactive oxygen species (72, 73).”
BackgroundDellero, Y., Cagnac, O., Rose, S. L., Seddiki, K., Cussac, M., Morabito, C., Lupette, J., Cigliano, R. A., Sanseverino, W., Kuntz, M., et al. (2018) · Algal Research · doi:10.1016/j.algal.2018.08.018 · Cited by 89 · see citing works
Zhang, Y., Wu, Y. F., Zhang, M., Li, Z., Liu, B., Liu, H.-F., Hao, J., & Li, X. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01353-w · Cited by 89 · see citing works
“Peroxisomemitochondria connections incorporate the metabolic cooperation of mitochondria and peroxisomes, such as the β-oxidation of fatty acids, phytanic acid α-oxidation, synthesis of bile acids and docosahexaenoic acids, glyoxylic acid metabolism, amino acid catabolism, polyamine oxidation, metabolism of ROS and ni…”
BackgroundPexophagy: Molecular Mechanisms and Implications for Health and Diseases.
Cho, D., Kim, Y. S., Jo, D. S., Choe, S., & Jo, E. (2018) · PubMed Central · doi:10.14348/molcells.2018.2245 · Cited by 85 · see citing works
“They are key metabolic platforms for purine catabolism, fatty acid beta-oxidation (FAO), bile acid synthesis, and ether phospholipid synthesis (Wanders et al., 2016).”
BackgroundHost-microbe co-metabolism via MCAD generates circulating metabolites including hippuric acid
Pruss, K. M., Chen, H., Liu, Y., Treuren, W. V., Higginbottom, S. K., Jarman, J. B., Fischer, C. R., Mak, J., Wong, B. T., Cowan, T. M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36138-3 · Cited by 92 · see citing works
Pascual‐Ahuir, A., Manzanares‐Estreder, S., & Proft, M. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/9860841 · Cited by 83 · see citing works
“The details of this metabolic cooperation have been summarized in excellent recent reviews [241, 242].”
Fracassi, A., Marcatti, M., Zolochevska, O., Tabor, N., Woltjer, R., Moreno, S., & Taglialatela, G. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.0295-20.2020 · Cited by 81 · see citing works
“…biogenesis (Austin and St-Pierre, 2012), a correlation between the oxidative stress observed in AD frontal cortices and dysfunctions of these organelles, likely because of PGC1a downregulation, could be hypothesized (Demarquoy and Le Borgne, 2015; Sweeney and Song, 2016; Wanders et al., 2016).”
BackgroundFatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity
Ježek, P., Jabůrek, M., Holendová, B., & Plecitá-Hlavatá, L. (2018) · Molecules · doi:10.3390/molecules23061483 · Cited by 78 · see citing works
“It has been reported that peroxisomes increase H2O2 formation responding to FAs [124,141], but they contain distinct enzymes for each particular step of β-oxidation and have different substrate specificities compared to mitochondria [142].”
BackgroundTumor diversity and the trade-off between universal cancer tasks
Hausser, J., Székely, P., Bar, N., Zimmer, A., Sheftel, H., Caldas, C., & Alon, U. (2019) · Nature Communications · doi:10.1038/s41467-019-13195-1 · Cited by 76 · see citing works
Maintaining social contacts: The physiological relevance of organelle interactions
Silva, B. S. C., DiGiovanni, L. F., Kumar, R., Carmichael, R. E., Kim, P. K., & Schrader, M. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2020.118800 · Cited by 81 · see citing works
Free radicals: Relationship to Human Diseases and Potential Therapeutic applications
Zarić, B. L., Mačvanin, M., & Isenović, E. R. (2022) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2022.106346 · Cited by 100 · see citing works
Debbabi, M., Zarrouk, A., Bezine, M., Meddeb, W., Nury, T., Badreddine, A., Karym, E. M., Sghaier, R., Brétillon, L., Guyot, S., et al. (2017) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2017.04.002 · Cited by 82 · see citing works
“…and other subcellular organelles, mitochondria and endoplasmic reticulum, which are targets of 7KC (Vejux and Lizard, 2009), the DHA-induced attenuation of peroxisomal damage might contribute to the attenuation of damage to 19 mitochondria and the endoplasmic reticulum (Wanders et al., 2015).”
BackgroundKawaguchi, K., & Morita, M. (2016) · BioMed Research International · doi:10.1155/2016/6786245 · Cited by 81 · see citing works
“Like the activity of mitochondrial β-oxidation, the β-oxidation performed in peroxisomes is conducted by oxidation, hydration, dehydrogenation, and thiolytic cleavage [23].”
BackgroundDikalov, S., & Dikalova, A. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7632 · Cited by 79 · see citing works
“Mitochondria can oxidize fatty acids all the way to CO2 and H2O; however, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal b-oxidation must be transported to mitochondria for full oxidation (117).”
BackgroundStrategies for organelle targeting of fluorescent probes
Lin, J., Yang, K., & New, E. J. (2021) · Organic & Biomolecular Chemistry · doi:10.1039/d1ob01447a · Cited by 82 · see citing works
Peroxisomal ACBD4 interacts with VAPB and promotes ER-peroxisome associations
Costello, J. L., Castro, I. G., Schrader, T. A., Islinger, M., & Schrader, M. (2017) · Cell Cycle · doi:10.1080/15384101.2017.1314422 · Cited by 79 · see citing works
“bond by peroxisomal enzymes before the remaining steps in biosynthesis can be completed in the ER.(4,5) Failure to properly assemble peroxisomes (e.”
Peroxisomal ABC Transporters: An Update
Tawbeh, A., Gondcaille, C., Trompier, D., & Savary, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116093 · Cited by 68 · see citing works
“In yeast and plants, this process of FA β-oxidation occurs exclusively in peroxisomes, whereas in higher eukaryotes, the catabolism of VLCFAs is initiated solely in the peroxisomes [7,80].”
BackgroundNervonic acid and its sphingolipids: Biological functions and potential food applications
Phung, N. V., Rong, F., Xia, W.-Y., Fan, Y., Li, X. Y., Wang, S. A., & Li, F. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2203753 · Cited by 72 · see citing works
“The energy metabolism or ATP synthesis of VLCFA molecules (e.g., NA) is an interplay process between the per-oxisome and mitochondria (Wanders, Waterham, and Ferdinandusse 2015). a.”
AHR is a master regulator of diverse pathways in endogenous metabolism
Granados, J. C., Falah, K., Koo, I., Morgan, E. W., Perdew, G. H., Patterson, A. D., Jamshidi, N., & Nigám, S. K. (2022) · Scientific Reports · doi:10.1038/s41598-022-20572-2 · Cited by 72 · see citing works
A tale of two lipids: Lipid unsaturation commands ferroptosis sensitivity
Rodencal, J. J., & Dixon, S. J. (2022) · PROTEOMICS · doi:10.1002/pmic.202100308 · Cited by 70 · see citing works
“It should also be noted that while most PUFAs are synthesized in the ER [107], the final step of docosahexaenoic (DHA, FA 22:6n–3) synthesis occurs in the peroxisome [108].”
BackgroundWanders, R. J. A., Visser, G., Ferdinandusse, S., Vaz, F. M., & Houtkooper, R. H. (2020) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2020.9.3.313 · Cited by 75 · see citing works
Self-citationXu, W., Vervoort, J. J. M., Saccenti, E., Kemp, B., van Hoeij, R. J., & van Knegsel, A. T. M. (2020) · Journal of Dairy Science · doi:10.3168/jds.2019-17777 · Cited by 70 · see citing works
“carnitine play important roles in transporting activated long-chain fatty acids from the cytosol into the peroxisome and mitochondria (Wanders et al., 2016).”
BackgroundWanders, R. J. A., Vaz, F. M., Waterham, H. R., & Ferdinandusse, S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-60204-8_5 · Cited by 67 · see citing works
Self-citationPeroxisomal plant metabolism – an update on nitric oxide, Ca2+ and the NADPH recycling network
Corpas, F. J., & Barroso, J. B. (2017) · Journal of Cell Science · doi:10.1242/jcs.202978 · Cited by 65 · see citing works
“…in the study of these organelles have revealed that they are extraordinary subcellular compartments characterized by great endogenous metabolic adaptability and highly active interactions with other subcellular compartments (van der Zand et al., 2006; Mast et al., 2015; Wanders et al., 2016).”
BackgroundDruggability of lipid metabolism modulation against renal fibrosis
Chen, Y., Chen, X., & Zhang, S. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00660-1 · Cited by 64 · see citing works
“With the help of a unilateral ischemia-reperfusion injury-induced kidney fibrosis model, researchers demonstrated that ATGFα in proximal renal tubular cells was activated and then moved into the nucleus, acting as an inhibitor of PPAR-α to reduce PPAR-α expression, then led to CPT2 (one target gene of PPAR-α) downregu…”
BackgroundInfluentialPeroxisomal dysfunction in neurodegenerative diseases
Jo, D. S., & Cho, D. (2019) · Archives of Pharmacal Research · doi:10.1007/s12272-019-01131-2 · Cited by 64 · see citing works
“DHA is synthesized from dietary linolenic acid through a cooperation of ER and peroxisome (Wanders et al. 2015).”
BackgroundThe Impacts of Herbal Medicines and Natural Products on Regulating the Hepatic Lipid Metabolism
Li, S., Xu, Y., Guo, W., Chen, F., Zhang, C., Tan, H. Y., Wang, N., & Feng, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00351 · Cited by 64 · see citing works
Deuterium-Depleted Water Influence on the Isotope 2H/1H Regulation in Body and Individual Adaptation
Басов, А. А., Fedulova, L., Baryshev, M., & Dzhimak, S. S. (2019) · Nutrients · doi:10.3390/nu11081903 · Cited by 63 · see citing works
“Moreover, the share of intracellular water synthesized de novo can reach more than 50% [32,33], that occurs with the active interaction of mitochondria, endoplasmic reticulum and peroxisome [34].”
BackgroundLaunay, N., Ruíz, M., Grau, L., Ortega, F. J., Ilieva, E. V., Martínez, J. J., Galea, E., Ferrer, I., Knecht, E., Pujol, A., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1655-9 · Cited by 63 · see citing works
“Peroxisomes are oxidative organelles present in all tissues and organisms [83, 84, 102, 103] and are involved in several anabolic and catabolic reactions, including the following: the degradation of long- and very long-chain fatty acids (LCFA, VLCFA (C ≥ 22:0), respectively) by α- or β-oxidation and hydrogen peroxide…”
BackgroundInfluentialCellular Compartmentation and the Redox/Nonredox Functions of NAD +
Kulkarni, C. A., & Brookes, P. S. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2018.7722 · Cited by 64 · see citing works
“We focus on the cytosolic, mitochondrial, and nuclear compartments, since these are the most studied, with NAD(H) in other compartments such as endoplasmic reticulum (ER) or peroxisomes being beyond the scope of this review [see (166) for review].”
BackgroundHuman milk microbiota associated with early colonization of the neonatal gut in Mexican newborns
Corona-Cervantes, K., García‐González, I., Villalobos-Flores, L. E., Hernández-Quiroz, F., Piña-Escobedo, A., Hoyo‐Vadillo, C., Rangel-Calvillo, M. N., & Garcı́a-Mena, J. (2020) · PeerJ · doi:10.7717/peerj.9205 · Cited by 62 · see citing works
Regulating peroxisome–ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β
Kors, S., Hacker, C., Bolton, C., Maier, R., Reimann, L., Kitchener, E. J. A., Warscheid, B., Costello, J. L., & Schrader, M. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202003143 · Cited by 58 · see citing works
Kuna, R. S., Kumar, A., Gálvez, H., Wessendorf-Rodriguez, K. A., Green, C. R., McGregor, G. H., Cordes, T., Shaw, R. J., Svensson, R. U., & Metallo, C. M. (2023) · Science Advances · doi:10.1126/sciadv.adf0138 · Cited by 61 · see citing works
Achar, P. N., Quyen, P. T. T., Adukwu, E. C., Sharma, A., Msimanga, H. Z., Nagaraja, H., & Sreenivasa, M. Y. (2020) · Journal of Fungi · doi:10.3390/jof6040383 · Cited by 63 · see citing works
Peroxisomal Stress Response and Inter-Organelle Communication in Cellular Homeostasis and Aging
Kim, J., & Bai, H. (2022) · Antioxidants · doi:10.3390/antiox11020192 · Cited by 64 · see citing works
“Peroxisomes are the major site for both the production and degradation of hydrogen peroxide (H2O2) due to their high content of peroxisomal oxidases and antioxidant enzymes, such as catalase.”
BackgroundInfluentialKumar, V., Singh, D. D., Lakhawat, S. S., Yasmeen, N., Pandey, A., & Singla, R. K. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/6852276 · Cited by 63 · see citing works
“)e obese individual tends to depend upon glucose oxidation more than fatty acid oxidation revealing that mitochondrial fatty acid oxidation is compromised [67].”
BackgroundRole of Fatty Acids β-Oxidation in the Metabolic Interactions Between Organs
Panov, A. V., Mayorov, V., & Dikalov, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312740 · Cited by 63 · see citing works
“Phytanic acid initially activates phytanyl CoA; then, phytanyl CoA hydroxylase ( α -hydroxylase), encoded by the PHYH gene, introduces a hydroxyl group to the alpha carbon [48].”
Lipids, lysosomes and mitochondria: insights into Lewy body formation from rare monogenic disorders
Erskine, D., Koss, D. J., Korolchuk, V. I., Outeiro, T. F., Attems, J., & McKeith, I. G. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02266-7 · Cited by 58 · see citing works
“For example, there is considerable evidence of mitochondrial respiratory chain dysfunction in LBD, but relatively little is known about peroxisomal function, despite their role in degrading very long chain fatty acids for mitochondrial β-oxidation and scavenging ROS placing them at a potentially pivotal juncture betwe…”
BackgroundHelf, M. J., Fox, B. W., Artyukhin, A. B., Zhang, Y. K., & Schroeder, F. C. (2022) · Nature Communications · doi:10.1038/s41467-022-28391-9 · Cited by 59 · see citing works
Chronic acidosis rewires cancer cell metabolism through PPARα signaling
Rolver, M. G., Holland, L. K. K., Ponniah, M., Prasad, N. S., Yao, J., Schnipper, J., Kramer, S. H., Elingaard-Larsen, L. O., Pedraz‐Cuesta, E., Liu, B., et al. (2022) · International Journal of Cancer · doi:10.1002/ijc.34404 · Cited by 58 · see citing works
“34 Accord-ingly, a striking number of peroxisomal genes were upregulated in AA cells, including Peroxisomal biogenesis factor 5 (PEX5), PEX11A, other PEX isoforms, and acyl-coenzyme A oxidase 1 (ACOX1), the main enzyme responsible for peroxisomal oxidation of VLCFAs 34 (Figures 3A and S6 and Tables S1 and S2).”
BackgroundInfluentialChirumbolo, S., & Bjørklund, G. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010165 · Cited by 55 · see citing works
“Furthermore, a metabolic interplay exists between peroxisomes and other intracellular organelles, whereby peroxisomes are involved in the ROS/RNS metabolism [60].”
BackgroundThe translational regulator FMRP controls lipid and glucose metabolism in mice and humans
Leboucher, A., Pisani, D. F., Martinez-Gili, L., Chilloux, J., Bermudez-Martin, P., Van Dijck, A., Ganief, T., Macek, B., Becker, J. A. J., Le Merrer, J., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.01.002 · Cited by 56 · see citing works
“Furthermore, overabundance of the FA transporter Abcd3 and of the aldehyde dehydrogenase Aldh3a2 could also be indicative of increased peroxisomal b-oxidation of lipids [53].”
BackgroundFarrugia, M. A., & Puglielli, L. (2018) · Journal of Cell Science · doi:10.1242/jcs.221747 · Cited by 52 · see citing works
“, 2001), the peroxisome (Wanders et al., 2015), the nucleus”
Che, X., Brydges, C. R., Yu, Y., Price, A., Joshi, S., Roy, A., Lee, B., Barupal, D. K., Cheng, A., Palmer, D. M., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23147906 · Cited by 51 · see citing works
“Peroxisomal β-oxidation of very long-chain fatty acids leads to their breakdown into short-chain products that serve as substrates for mitochondrial β-oxidation [34].”
BackgroundNury, T., Sghaier, R., Zarrouk, A., Ménétrier, F., Uzun, T., Leoni, V., Caccia, C., Meddeb, W., Namsi, A., Sassi, K., et al. (2018) · Biochimie · doi:10.1016/j.biochi.2018.07.009 · Cited by 54 · see citing works
Bülow, M. H., Wingen, C., Senyilmaz, D., Gosejacob, D., Sociale, M., Bauer, R., Schulze, H., Sandhoff, K., Teleman, A. A., Hoch, M., et al. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-08-0535 · Cited by 52 · see citing works
“…measured as the amount of oxygen consumption (in the presence of palmitoyl-CoA substrate, the necessary TCA cycle intermediates, and ADP, i.e., state 3 respiration) that is sensitive to etomoxir, a standard carnitine palmitoyl transferase (CPT-I) inhibitor (Kuznetsov et al., 2008; Xu et al., 2012).”
BackgroundPI5P4Ks drive metabolic homeostasis through peroxisome-mitochondria interplay
Ravi, A., Palamiuc, L., Loughran, R. M., Triscott, J., Arora, G. K., Kumar, A., Tieu, V., Pauli, C., Reist, M., Lew, R. J., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.04.019 · Cited by 53 · see citing works
Ghareghani, M., Scavo, L., Jand, Y., Farhadi, N., Sadeghi, H., Ghanbari, A., Mondello, S., Arnoult, D., Gharaghani, S., & Zibara, K. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00147 · Cited by 48 · see citing works
“Indeed, FAs are converted to acetyl-carnitine which is then exported to cytosol where it can be converted to acetyl-CoA, to be used again as a substrate in FA and cholesterol synthesis (Wanders et al., 2015).”
BackgroundMolecular insights into peroxisome homeostasis and peroxisome biogenesis disorders
Fujiki, Y., Okumoto, K., Honsho, M., & Abe, Y. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2022.119330 · Cited by 47 · see citing works
Intracellular to Interorgan Mitochondrial Communication in Striated Muscle in Health and Disease
Boardman, N. T., Trani, G., Scalabrin, M., Romanello, V., & Wüst, R. C. I. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad004 · Cited by 49 · see citing works
Coconut-sourced MCT oil: its potential health benefits beyond traditional coconut oil
Ďúranová, H., Kuželová, L., Fialková, V., Šimora, V., Kováčiková, E., Joanidis, P., Borotová, P., Straka, D., Hoskin, R. T., Moncada, M. L., et al. (2024) · Phytochemistry Reviews · doi:10.1007/s11101-024-09969-1 · Cited by 56 · see citing works
“However, these subcellular organelles depend on cooperation with mitochondria, as they receive the end products of peroxisomal b - oxidation for complete degradation to CO 2 and H 2 O (Wanders et al. 2016).”
Peroxisomes: role in cellular ageing and age related disorders
Deori, N. M., Kale, A., Maurya, P. K., & Nagotu, S. (2018) · Biogerontology · doi:10.1007/s10522-018-9761-9 · Cited by 47 · see citing works
Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts
Missailidis, D., Sanislav, O., Allan, C. Y., Smith, P. K., Annesley, S. J., & Fisher, P. R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042046 · Cited by 46 · see citing works
“Acyl-CoA oxidase 1 (ACOX1) is the enzyme which first initiates VLCFA β-oxidation inside the peroxisome and is the rate-controlling enzyme of this process [50].”
BackgroundInfluentialDirect androgen receptor control of sexually dimorphic gene expression in the mammalian kidney
Xiong, L., Liu, J., Han, S. Y., Koppitch, K. A., Guo, J., Rommelfanger, M. K., Miao, Z., Gao, F., Hallgrímsdóttir, I. B., Pachter, L. S., et al. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.08.010 · Cited by 43 · see citing works
Fatty Liver Due to Increased de novo Lipogenesis: Alterations in the Hepatic Peroxisomal Proteome
Knebel, B., Fahlbusch, P., Dille, M. A., Wahlers, N., Hartwig, S., Jacob, S., Kettel, U., Schiller, M., Herebian, D. A., Koellmer, C., et al. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00248 · Cited by 44 · see citing works
“It is well known that mitochondria have a central role in lipid-degrading, but the metabolic function of peroxisomes is also becoming more important in order to counteract lipid accumulation in hepatocytes during metabolic stress (Unger et al., 2010; Fransen et al., 2012; Wanders, 2013; Knebel et al., 2015, 2018a; Wan…”
BackgroundEaston, Z. J. W., & Regnault, T. R. H. (2020) · Nutrients · doi:10.3390/nu12103031 · Cited by 44 · see citing works
“In brief, peroxisomal beta-oxidation shortens long-chain FA species into acetyl-CoA and short-chain acyl-CoAs such as octanoyl-CoA which can then be exported into the mitochondria for complete oxidation [99,101].”
BackgroundStay in touch with the endoplasmic reticulum
Sun, S., Gan, Z., Jia, M., Jiang, Q., Li, S., Wang, H., Li, W., Wang, Y., Bian, X., Zhao, Y. G., et al. (2024) · Science China Life Sciences · doi:10.1007/s11427-023-2443-9 · Cited by 43 · see citing works
“In addition, ROS signaling has been observed in the ER, mitochondria, and peroxisome, with these three organelles forming the intriguing “ redox triangle ” (Wanders et al., 2016), an entity that is evidently contact-dependent.”
BackgroundRuiz, M., Cuillerier, A., Daneault, C., Deschênes, S., Frayne, I. R., Bouchard, B., Forest, A., Legault, J. T., Vaz, F. M., Rioux, J. D., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.123231 · Cited by 44 · see citing works
“…obtained in the nutrient-uptake challenge condition. with a very-long-chain (VLCFAs; >20 C), which cannot be oxidized by mitochondria, or with an odd chain, generated from dietary phytanic acid metabolism (18), and (ii) C24 BAs conjugated with glycine (glyco-BA) or taurine (tauro-BA) (19, 26).”
BackgroundMethodInfluentialStaying in Healthy Contact: How Peroxisomes Interact with Other Cell Organelles
Sargsyan, Y., & Thoms, S. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.09.012 · Cited by 44 · see citing works
Wright, Z. J., & Bartel, B. (2020) · Nature Communications · doi:10.1038/s41467-020-20099-y · Cited by 43 · see citing works
Biochemistry, Fatty Acid Oxidation
Talley, J. T., & Mohiuddin, S. S. (2021) · StatPearls · Cited by 42 · see citing works
Genome‐wide characterization of Phytophthora infestans metabolism: a systems biology approach
Rodenburg, S. Y. A., Seidl, M. F., de Ridder, D., & Govers, F. (2017) · Molecular Plant Pathology · doi:10.1111/mpp.12623 · Cited by 38 · see citing works
“There is an extensive exchange of metabolites between subcellular compartments (Wanders et al., 2016).”
Multi-localized Proteins: The Peroxisome-Mitochondria Connection
Costello, J. L., Passmore, J. B., Islinger, M., & Schrader, M. (2018) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-981-13-2233-4_17 · Cited by 38 · see citing works
Kingsmore, K. M., Bachali, P., Catalina, M. D., Daamen, A. R., Heuer, S. E., Robl, R. D., Grammer, A. C., & Lipsky, P. E. (2021) · Scientific Reports · doi:10.1038/s41598-021-93034-w · Cited by 40 · see citing works
Determinants of Peroxisome Membrane Dynamics
Carmichael, R. E., & Schrader, M. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.834411 · Cited by 38 · see citing works
Passmore, J. B., Pinho, S., Gómez-Lázaro, M., & Schrader, M. (2017) · Histochemistry and Cell Biology · doi:10.1007/s00418-017-1577-1 · Cited by 38 · see citing works
L-Carnitine in Drosophila: A Review
Carillo, M. R., Bertapelle, C., Scialò, F., Siervo, M., Spagnuolo, G., Simeone, M., Peluso, G., & Digilio, F. A. (2020) · Antioxidants · doi:10.3390/antiox9121310 · Cited by 37 · see citing works
- Authors
- Wanders, R. J. A., Waterham, H. R., & Ferdinandusse, S.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Wanders, Ronald J. A.
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2016-01-28
- Volume
- 3
- Pages
- 83-83
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC4729952
- OpenAlex
- W2262335045
- Cited by
- 366
- References
- 88
- Citations by year
- 2026: 25 · 2025: 36 · 2024: 43 · 2023: 31 · 2022: 56 · 2021: 39 · 2020: 50 · 2019: 30 · 2018: 29 · 2017: 24 · 2016: 2 · 2012: 1
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- European Commission (316723)
- Hersenstichting (F2012(1)-102)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- peroxisomes, fatty acid beta-oxidation, NADH reoxidation, bile acid synthesis, glyoxylate metabolism, amino acid catabolism
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