Impaired phosphatidylethanolamine metabolism activates a reversible stress response that detects and resolves mutant mitochondrial precursors
Year: 2021
Type: article
Abstract: Phosphatidylethanolamine (PE) made in mitochondria has long been recognized as an important precursor for phosphatidylcholine production that occurs in the endoplasmic reticulum (ER). Recently, the strict mitochondrial localization of the enzyme that makes PE in the mitochondrion, phosphatidylserine decarboxylase 1 (Psd1), was questioned. Since a dual localization of Psd1 to the ER would have far-reaching implications, we initiated our study to independently re-assess the subcellular distribution of Psd1. Our results support the unavoidable conclusion that the vast majority, if not all, of functional Psd1 resides in the mitochondrion. Through our efforts, we discovered that mutant forms of Psd1 that impair a self-processing step needed for it to become functional are dually localized to the ER when expressed in a PE-limiting environment. We conclude that severely impaired cellular PE metabolism provokes an ER-assisted adaptive response that is capable of identifying and resolving nonfunctional mitochondrial precursors.
Source: iScience
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funders: National Science Foundation, Pew Charitable Trusts, American Heart Association, Indiana University, University of Texas Southwestern Medical Center, Sociedad Española de Nefrología, National Institutes of Health, Office of the Director, University of California, Los Angeles, University of California, Davis, Canadian Institutes of Health Research, Japan Society for the Promotion of Science, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences
Awards: Mitochondrial phosphatidylethanolamine metabolism, G1467323428, G1473319671, Replacement of Small Animal Echocardiographic Instrumentation, G2340616118, G2911662409, G3467391522, Biochemistry, Cellular and Molecular Biology Program, G4552790918, Graduate Research Fellowship Program (GRFP), Structural biology of the mechanism of biomembrane phospholipid biosynthesis by phosphatidylserine decarboxylase, G8205493998, A Molecular Understanding of Sengers Syndrome, G9000027872, Training in Cardiovascular Physiology and Pharmacology, The Discovery of Molecules and Mechanisms of the Rhomboid Superfamily, UCSD Future Faculty of Cardiovascular Sciences (FOCUS)
OpenAlex ID: W3132010583