A robust, integrated platform for comprehensive analyses of acyl-coenzyme As and acyl-carnitines revealed chain length-dependent disparity in fatty acyl metabolic fates across Drosophila development
| Autor: | Guanghou Shui, Bowen Li, Shaohua Zhang, Gek Huey Chua, Tianxing Zhou, Jie Li, Sin Man Lam |
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| Rok vydání: | 2020 |
| Předmět: |
Multidisciplinary
biology Anabolism Catabolism Chemistry Endogeny Mitochondrion 010502 geochemistry & geophysics biology.organism_classification 01 natural sciences Cell biology Metabolic pathway Mitochondrial matrix lipids (amino acids peptides and proteins) Drosophila Function (biology) 0105 earth and related environmental sciences |
| Zdroj: | Science Bulletin. 65:1840-1848 |
| ISSN: | 2095-9273 |
| Popis: | Acyl-coenzyme A thioesters (acyl-CoAs) denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways. The great diversity in polarity between short- and long-chain acyl-CoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method. Levels of acyl-carnitines, which function to convey fatty acyls into mitochondria matrix for β-oxidation, indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs. Herein, we report a robust, integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines. Using this method, we monitored changes in intermediary lipid profiles across Drosophila development under control (ND) and high-fat diet (HFD). We observed specific accumulations of medium-chain (C8–C12) and long-chain (≥C16) acyl-carnitines distinct to L3 larval and pupal stages, respectively. These observations suggested development-specific, chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development, which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra- and intra-mitochondrial acyl-CoA pools. We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs (accumulated as C12:0-carnitines in L3 stage) over C16:0-CoAs. Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs (C16–C18), leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6A activity. HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa, thereby adversely affecting overall development. Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems. |
| Databáze: | OpenAIRE |
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