Molecular mechanism and physiological role of pexophagy

Abstract

a b s t r a c tPexophagy is a selective autophagy process wherein damaged and/or superfluous peroxisomes undergo vacuolar degradation. In methylotropic yeasts, where pexophagy has been studied most extensively, this process occurs by either micro-or macropexophagy: processes analogous to microand macroautophagy. Recent studies have identified specific factors and illustrated mechanisms involved in pexophagy. Although mechanistically pexophagy relies heavily on the core autophagic machinery, the latest findings about the role of auxiliary pexophagy factors have highlighted specialized membrane structures required for micropexophagy, and shown how cargo selectivity is achieved and how cargo size dictates the requirement for these factors during pexophagy. These insights and additional observations in the literature provide a framework for an understanding of the physiological role(s) of pexophagy.

Interaction of Phospholipase A/Acyltransferase-3 with Pex19p

“…Thus, it appeared that the expression level of PLA/AT-3, increasing PLA 1 /A 2 activity 10-fold over the control cells, is sufficient to see the loss of peroxisomes. It has been reported that the quality and quantity of peroxisomes are maintained by peroxisome-specific autophagy, pexophagy (11,13). However, during the DOX-dependent reduction of peroxisomes, the activation of LC3, a marker of autophagy, was not observed.…”

“…However, we could not rule out the possibility that the expression levels of these proteins were not high enough to overcome the effect of PLA/AT-3 on peroxisomal structure. Our finding might result from the enhanced clearance of peroxisomes by the selective autophagy "pexophagy" (11,13,35). We therefore examined whether PLA/AT-3 stimulates the conversion of LC3-I protein to its phosphatidylethanolamineconjugated form, LC3-II, which is known to occur during autophagosome formation (36).…”

“…Metabolic Labeling-Cells were grown at 37°C to 80% confluence in a 6-well plate containing Dulbecco's modified Eagle's medium with 10% fetal calf serum and were labeled with [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]hexadecanol (1.6 Ci) for 18 h. Cells were then harvested and washed twice with PBS. The total lipids were extracted by the method of Bligh and Dyer (29), spotted on a silica gel thin layer plate (20-cm height), and developed at 4°C for 1 h in hexane/diethyl ether/acetic acid (75:25:1, v/v/v).…”

“…These results indicate that peroxisome levels are reciprocally regulated by the balance between their biogenesis and degradation. Recently, it has been reported that the selective autophagy of peroxisomes, pexophagy, contributes to the maintenance of quality and quantity of peroxisomes (11,13).…”

Protein Folding and Quality Control in the ER

“…Hence, the ER and the process of autophagy would certainly have a tight physiological relationship. Organelles are also selectively delivered to lysosomes by macroautophagy, known as ERphagy (reticulophagy), mitophagy, or pexophagy (Kim et al 2007;Yorimitsu and Klionsky 2007a;Ding and Yin 2008;Todde et al 2009;Manjithaya et al 2010).…”