Autophagy of an oxidized, aggregated protein beyond the ER: a pathway for remarkably late-stage quality control.
The authors recently reported a novel role for autophagy in late-stage quality control of a secreted protein, apolipoprotein-B(100) (apoB). Hepatocytes assemble this protein with triglycerides, cholesterol and other lipids into macromolecular complexes called lipoproteins. In what appears to be a normal response to diets rich in polyunsaturated fatty acids, which are readily peroxidized, apoB comes into contact with lipid peroxides in or after the Golgi apparatus. The protein becomes oxidatively damaged, aggregates, and is diverted out of the secretory pathway by autophagosomes, which deliver it to lysosomes for destruction. ApoB secretory control via autophagosomes is likely a key component of normal and pathological regulation of plasma lipoprotein levels, as well as a means for remarkably late-stage quality control of a secreted protein.
Department of Medicine, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, New York 10016, USA. edward.fisher@med.nyu.edu
Edward A
EA
Fisher
Kevin Jon
KJ
Williams
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism* / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
D001055:Apolipoproteins B; D005231:Fatty Acids, Unsaturated