Smith Danielle M, Choi Joseph, Wolfgang Michael J
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Adv Biol Regul. 2025 Jan;95:101070. doi: 10.1016/j.jbior.2024.101070. Epub 2024 Dec 5.
Mitochondrial long chain fatty acid β-oxidation is a critical central carbon catabolic process. The importance of fatty acid oxidation is made evident by the life-threatening disease associated with diverse inborn errors in the pathway. While inborn errors show multisystemic requirements for fatty acid oxidation, it is not clear from the clinical presentation of these enzyme deficiencies what the tissue specific roles of the pathway are compared to secondary systemic effects. To understand the cell or tissue specific contributions of fatty acid oxidation to systemic physiology, conditional knockouts in mice have been employed to determine the requirements of fatty acid oxidation in disparate cell types. This has produced a host of surprising results that sometimes run counter to the canonical view of this metabolic pathway. The rigor of conditional knockouts has also provided clarity over previous research utilizing cell lines in vitro or small molecule inhibitors with dubious specificity. Here we will summarize current research using mouse models of Carnitine Palmitoyltransferases to determine the tissue specific roles and requirements of long chain mitochondrial fatty acid β-oxidation.
线粒体长链脂肪酸β-氧化是一种关键的中心碳分解代谢过程。脂肪酸氧化的重要性在与该途径中多种先天性代谢缺陷相关的危及生命的疾病中得以体现。虽然先天性代谢缺陷显示出对脂肪酸氧化的多系统需求，但从这些酶缺乏症的临床表现中尚不清楚该途径的组织特异性作用与继发性全身效应相比如何。为了了解脂肪酸氧化对全身生理的细胞或组织特异性贡献，已在小鼠中采用条件性基因敲除来确定不同细胞类型中脂肪酸氧化的需求。这产生了一系列令人惊讶的结果，有时与这种代谢途径的传统观点相悖。条件性基因敲除的严谨性也为先前使用体外细胞系或特异性存疑的小分子抑制剂的研究提供了清晰的认识。在此，我们将总结目前使用肉碱棕榈酰转移酶小鼠模型的研究，以确定长链线粒体脂肪酸β-氧化的组织特异性作用和需求。
