Pex24 and Pex32 tether peroxisomes to the ER for organelle biogenesis, positioning and segregation

Abstract

Two Hansenula polymorpha ER proteins, Pex24 and Pex32, are tethers at peroxisome-ER contacts and function together with the peroxisomal protein Pex11. Their absence disturbs these contacts leading to multiple peroxisomal defects, which can be restored by an artificial tether. AbstractWe analyzed all four Pex23 family proteins of the yeast Hansenula polymorpha, which localize to the ER. Of these Pex24 and Pex32, but not Pex23 and Pex29, accumulate at peroxisome-ER contacts, where they are important for normal peroxisome biogenesis and proliferation and contribute to organelle positioning and segregation.Upon deletion of PEX24 and PEX32 -and to a lesser extent of PEX23 and PEX29peroxisome-ER contacts are disrupted, concomitant with peroxisomal defects. These defects are suppressed upon introduction of an artificial peroxisome-ER tether.

Peroxisome retention involves Inp1-dependent peroxisome–plasma membrane contact sites in yeast

“…3 D ). In line with our earlier observations, peroxisome–ER contacts require Pex32 ( Wu et al, 2020 ). The distance between peroxisomes and ER increased in the absence of Pex32, whereas associations with the PM were unaffected in these cells ( Fig.…”

Maintaining social contacts: The physiological relevance of organelle interactions

“…Similar observations have recently been made in the yeast Hansenula polymorpha [ 146 ]. This study revealed that the peroxins Pex24 and Pex32, which localize to the ER, function as tethers to mediate peroxisome-ER contacts ( Table 1 ).…”

“…While the functions of MOSPD2 are not clear and its effect on MCSs is not understood, it is possible that, like VAP proteins, MOSPD2 also interacts with ACBD4/5, so may represent a novel peroxisome-ER tether [ 16 ]. In yeast, the peroxins Pex3, Pex24, Pex32 and the inheritance protein Inp1 have been implicated in peroxisome-ER tethering (see Section 3.1.2 ) [ 3 , [146] , [147] , [148] ] ( Table 1 ).…”

“…Interestingly, accumulation of Pex32 at peroxisome-ER contacts was lost in the absence of the peroxisomal membrane protein Pex11 ( Table 1 ). Additionally, peroxisome-ER contacts were disrupted, indicating that Pex11 functions together with Pex23 family proteins to associate peroxisomes to the ER [ 146 ]. S .…”

“… [ 164 ] Pex34(PO), Fzo1 (MITO) tether (yeast) Regulation of fatty acid β-oxidation in yeast (metabolite transfer) [ 7 ] ACBD2 (PO/MITO) Promotion of steroid biosynthesis (Leydig cells) [ 193 ] Peroxisomes – lysosomes/endosomes PI(4,5)P 2 (PO) – SYT7 (LYS) tether Cholesterol transport from LYS to PO [ 207 ] TMEM135 (PO) Cholesterol transport; intracellular cholesterol distribution; regulation of ciliogenesis (cholesterol dependent) [ 204 ] PxdA (ENDO) (fungi) PO movement via endosome ‘hitch-hiking’ [ 213 , 214 ] Pex3 (PO - vacuole) tether (yeast) PO growth/expansion; lipid transfer? [ 146 ] Golgi complex – endoplasmic reticulum PI(4)P (TGN) – OSBP1/ORP9/10/11 – VAP (ER) Direct transport of sterols [ 20 , 219 , [222] , [223] , [224] ] PI(4)P (TGN) – CERT – VAP (ER) Translocation of ceramide from the ER to TGN [ 218 , 226 ] PI(4)P (TGN) – FAPP1 – SAC1 (ER) – VAP (ER) PI4P homeostasis [ 228 ] Plasma membrane – endoplasmic reticulum Osh2/3/6/7 (PM) Osh2/3 (PM) – VAP (ER) tether (?) (yeast) Transport of sterols from the ER to the PM in yeast [ 233 ] Scs2/Scs22 (ER), Sac1 (ER), Ist2 (ER), Tcb1/2/3 (ER) (yeast) Phosphoinositide metabolism in yeast [ 238 ] NIR2 C2CD2L/TMEM24 Phosphatidylinositol transport between the ER and the PM.…”