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Role of protein phosphatase 2A in modulating autophagy and mitophagy (LB220)
Author(s) -
Rice Monica,
Dagda Ruben,
Strack Stefan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb220
Subject(s) - mitophagy , protein phosphatase 2 , autophagy , microbiology and biotechnology , protein subunit , mitochondrion , lysosome , cytosol , biology , parkin , chemistry , phosphatase , apoptosis , biochemistry , phosphorylation , gene , parkinson's disease , medicine , disease , pathology , enzyme
Protein phosphatase 2A (PP2A) is a holoenzyme composed of a scaffolding/catalytic dimer that binds to a regulatory (B) subunit which dictates subcellular targeting and substrate specificity of PP2A. The PP2A holoenzymes that modulate autophagy and mitophagy in neurons are not known to date. Bβ2 is a regulatory subunit that redirects PP2A from the cytosol to the mitochondrion to induce mitochondrial fission and apoptosis of neurons. Given that mitochondrial fission precedes mitophagy, we surmised that Bβ2 regulates mitophagy in neurons. To address this hypothesis, we used a combination of cell imaging and biochemical approaches to quantify autophagy and mitophagy in SH‐SY5Y cells transiently expressing the cytosolic regulatory subunit Bβ1 and the mitochondrial regulatory subunits Bβ2 and B56α. Western blot analyses showed that all three PP2A holoenzymes decrease the levels of the autophagosome marker microtubule‐associated protein 1 light chain 3 (LC3‐II) and prevent further increases in LC3‐II as induced by bafilomycin, a drug used to measure autophagic flux. Although all PP2A holoenzymes decrease the number of GFP tagged LC3 (GFP‐LC3) puncta per cell, confocal analyses show that Bβ2 increases the colocalization GFP‐LC3 puncta with mitochondria. Similar results were observed in COS‐7 cells. Our results suggest that PP2A decreases autophagic flux while PP2A/ Bβ2 promotes mitophagy. Grant Funding Source : P20 GM103554