Abstract
A recent report from the Laboratory of Heidi McBride (McGill University) presents a role for mitochondria in the de novo biogenesis of peroxisomes in mammalian cells. Peroxisomes are essential organelles responsible for a wide variety of biochemical functions, from the generation of bile to plasmalogen synthesis, reduction of peroxides, and the oxidation of very-long-chain fatty acids. Like mitochondria, peroxisomes proliferate primarily through growth and division of pre-existing peroxisomes. However, unlike mitochondria, peroxisomes do not fuse; further, and perhaps most importantly, they can also be born de novo, a process thought to occur through the generation of pre-peroxisomal vesicles that originate from the endoplasmic reticulum. De novo peroxisome biogenesis has been extensively studied in yeast, with a major focus on the role of the ER in this process; however, in the mammalian system this field is much less explored. By exploiting patient cells lacking mature peroxisomes, the McBride laboratory now assigns a role to ER and mitochondria in de novo mammalian peroxisome biogenesis by showing that the formation of immature pre-peroxisomes occurs through the fusion of Pex3-/Pex14-containing mitochondria-derived vesicles with Pex16-containing ER-derived vesicles.
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References
Sugiura A, Mattie S, Prudent J, McBride HM . Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes. Nature 2017; 542: 251–254.
Wanders RJ . Peroxisomes in human health and disease: metabolic pathways, metabolite transport, interplay with other organelles and signal transduction. Subcell Biochem 2013; 69: 23–44.
Lazarow PB, Fujiki Y . Biogenesis of peroxisomes. Annu Rev Cell Biol 1985; 1: 489–530.
Motley AM, Hettema EH . Yeast peroxisomes multiply by growth and division. J Cell Biol 2007; 178: 399–410.
Huybrechts SJ, Van Veldhoven PP, Brees C, Mannaerts GP, Los GV, Fransen M . Peroxisome dynamics in cultured mammalian cells. Traffic 2009; 10: 1722–1733.
Schrader M, Costello JL, Godinho LF, Azadi AS, Islinger M . Proliferation and fission of peroxisomes - an update. Biochim Biophys Acta 2016; 1863: 971–983.
Bonekamp NA, Sampaio P, de Abreu FV, Luers GH, Schrader M . Transient complex interactions of mammalian peroxisomes without exchange of matrix or membrane marker proteins. Traffic 2012; 13: 960–978.
Agrawal G, Subramani S . De novo peroxisome biogenesis: evolving concepts and conundrums. Biochim Biophys Acta 2016; 1863: 892–901.
Hua R, Kim PK . Multiple paths to peroxisomes: mechanism of peroxisome maintenance in mammals. Biochim Biophys Acta 2016; 1863: 881–891.
Kim PK, Mullen RT, Schumann U, Lippincott-Schwartz J . The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER. J Cell Biol 2006; 173: 521–532.
Delille HK, Agricola B, Guimaraes SC, Borta H, Luers GH, Fransen M et al. Pex11pbeta-mediated growth and division of mammalian peroxisomes follows a maturation pathway. J Cell Sci 2010; 123: 2750–2762.
Koch J, Pranjic K, Huber A, Ellinger A, Hartig A, Kragler F et al. PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance. J Cell Sci 2010; 123: 3389–3400.
Smith JJ, Aitchison JD . Peroxisomes take shape. Nat Rev Mol Cell Biol 2013; 14: 803–817.
Yuan W, Veenhuis M, van der Klei IJ . The birth of yeast peroxisomes. Biochim Biophys Acta 2016; 1863: 902–910.
van der Zand A, Gent J, Braakman I, Tabak HF . Biochemically distinct vesicles from the endoplasmic reticulum fuse to form peroxisomes. Cell 2012; 149: 397–409.
Knoops K, Manivannan S, Cepinska MN, Krikken AM, Kram AM, Veenhuis M et al. Preperoxisomal vesicles can form in the absence of Pex3. J Cell Biol 2014; 204: 659–668.
Motley AM, Galvin PC, Ekal L, Nuttall JM, Hettema EH . Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis. J Cell Biol 2015; 211: 1041–1056.
Hettema EH, Erdmann R, van der Klei I, Veenhuis M . Evolving models for peroxisome biogenesis. Curr Opin Cell Biol 2014; 29: 25–30.
Honsho M, Tamura S, Shimozawa N, Suzuki Y, Kondo N, Fujiki Y . Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D. Am J Hum Genet 1998; 63: 1622–1630.
Kiel JA, Veenhuis M, van der Klei IJ . PEX genes in fungal genomes: common, rare or redundant. Traffic 2006; 7: 1291–1303.
Matsuzaki T, Fujiki Y . The peroxisomal membrane protein import receptor Pex3p is directly transported to peroxisomes by a novel Pex19p- and Pex16p-dependent pathway. J Cell Biol 2008; 183: 1275–1286.
Muntau AC, Mayerhofer PU, Paton BC, Kammerer S, Roscher AA . Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. Am J Hum Genet 2000; 67: 967–975.
Hoepfner D, Schildknegt D, Braakman I, Philippsen P, Tabak HF . Contribution of the endoplasmic reticulum to peroxisome formation. Cell 2005; 122: 85–95.
Sacksteder KA, Jones JM, South ST, Li X, Liu Y, Gould SJ . PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis. J Cell Biol 2000; 148: 931–944.
Neuspiel M, Schauss AC, Braschi E, Zunino R, Rippstein P, Rachubinski RA et al. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Curr Biol 2008; 18: 102–108.
Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis MP, Wisniewski HK et al. Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science 1973; 182: 62–64.
Klouwer FC, Berendse K, Ferdinandusse S, Wanders RJ, Engelen M, Poll-The BT . Zellweger spectrum disorders: clinical overview and management approach. Orphanet J Rare Dis 2015; 10: 151.
Gould SJ, Valle D . Peroxisome biogenesis disorders: genetics and cell biology. Trends Genet 2000; 16: 340–345.
Erdmann R . Assembly, maintenance and dynamics of peroxisomes. Biochim Biophys Acta 2016; 1863: 787–789.
Soubannier V, McLelland GL, Zunino R, Braschi E, Rippstein P, Fon EA et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol 2012; 22: 135–141.
Rucktaschel R, Halbach A, Girzalsky W, Rottensteiner H, Erdmann R . De novo synthesis of peroxisomes upon mitochondrial targeting of Pex3p. Eur J Cell Biol 2010; 89: 947–954.
Yamashita S, Abe K, Tatemichi Y, Fujiki Y . The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy. Autophagy 2014; 10: 1549–1564.
Knoblach B, Rachubinski RA . How peroxisomes partition between cells. A story of yeast, mammals and filamentous fungi. Curr Opin Cell Biol 2016; 41: 73–80.
Williams C, van der Klei IJ . Pexophagy-linked degradation of the peroxisomal membrane protein Pex3p involves the ubiquitin-proteasome system. Biochem Biophys Res Commun 2013; 438: 395–401.
Platta HW, El Magraoui F, Schlee D, Grunau S, Girzalsky W, Erdmann R . Ubiquitination of the peroxisomal import receptor Pex5p is required for its recycling. J Cell Biol 2007; 177: 197–204.
Braschi E, Goyon V, Zunino R, Mohanty A, Xu L, McBride HM . Vps35 mediates vesicle transport between the mitochondria and peroxisomes. Curr Biol 2010; 20: 1310–1315.
Sugiura A, McLelland GL, Fon EA, McBride HM . A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J 2014; 33: 2142–2156.
McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA . Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J 2014; 33: 282–295.
McLelland GL, Lee SA, McBride HM, Fon EA . Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system. J Cell Biol 2016; 214: 275–291.
Matheoud D, Sugiura A, Bellemare-Pelletier A, Laplante A, Rondeau C, Chemali M et al. Parkinson's disease-related proteins PINK1 and parkin repress mitochondrial antigen presentation. Cell 2016; 166: 314–327.
Caielli S, Athale S, Domic B, Murat E, Chandra M, Banchereau R et al. Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus. J Exp Med 2016; 213: 697–713.
Schrader M, Yoon Y . Mitochondria and peroxisomes: are the 'big brother' and the 'little sister' closer than assumed? Bioessays 2007; 29: 1105–1114.
Bagattin A, Hugendubler L, Mueller E . Transcriptional coactivator PGC-1alpha promotes peroxisomal remodeling and biogenesis. Proc Natl Acad Sci USA 2010; 107: 20376–20381.
Berger J, Moller DE . The mechanisms of action of PPARs. Annu Rev Med 2002; 53: 409–435.
Costello JL, Castro IG, Hacker C, Schrader TA, Metz J, Zeuschner D et al. ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER. J Cell Biol 2017; 216: 331–342.
Hua R, Cheng D, Coyaud E, Freeman S, Di Pietro E, Wang Y et al. VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis. J Cell Biol 2017; 216: 367–377.
Stoica R, De Vos KJ, Paillusson S, Mueller S, Sancho RM, Lau KF et al. ER-mitochondria associations are regulated by the VAPB-PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nat Commun 2014; 5: 3996.
Giacomello M, Pellegrini L . The coming of age of the mitochondria-ER contact: a matter of thickness. Cell Death Differ 2016; 23: 1417–1427.
Sood A, Jeyaraju DV, Prudent J, Caron A, Lemieux P, McBride HM et al. A mitofusin-2-dependent inactivating cleavage of Opa1 links changes in mitochondria cristae and ER contacts in the postprandial liver. Proc Natl Acad Sci USA 2014; 111: 16017–16022.
Braverman NE, Moser AB . Functions of plasmalogen lipids in health and disease. Biochim Biophys Acta 2012; 1822: 1442–1452.
Herrera-Cruz MS, Simmen T . Of yeast, mice and men: MAMs come in two flavors. Biol Direct 2017; 12: 3.
Vance JE . Phospholipid synthesis in a membrane fraction associated with mitochondria. J Biol Chem 1990; 265: 7248–7256.
Vance JE . Newly made phosphatidylserine and phosphatidylethanolamine are preferentially translocated between rat liver mitochondria and endoplasmic reticulum. J Biol Chem 1991; 266: 89–97.
Vance JE . MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochim Biophys Acta 2014; 1841: 595–609.
Schrader M, Costello J, Godinho LF, Islinger M . Peroxisome-mitochondria interplay and disease. J Inherit Metab Dis 2015; 38: 681–702.
Pickrell AM, Youle RJ . The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. Neuron 2015; 85: 257–273.
Area-Gomez E, Del Carmen Lara Castillo M, Tambini MD, Guardia-Laguarta C, de Groof AJ, Madra M et al. Upregulated function of mitochondria-associated ER membranes in Alzheimer disease. EMBO J 2012; 31: 4106–4123.
Area-Gomez E, Schon EA . Mitochondria-associated ER membranes and Alzheimer disease. Curr Opin Genet Dev 2016; 38: 90–96.
Vyas S, Zaganjor E, Haigis MC . Mitochondria and Cancer. Cell 2016; 166: 555–566.
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We are grateful to Emma Clara Pellegrini for drawing the artwork shown in Figure 1.
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Schrader, M., Pellegrini, L. The making of a mammalian peroxisome, version 2.0: mitochondria get into the mix. Cell Death Differ 24, 1148–1152 (2017). https://doi.org/10.1038/cdd.2017.23
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DOI: https://doi.org/10.1038/cdd.2017.23
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