代替トリグリセリド生物合成経路の特定
Gian-Luca McLelland1, Marta Lopez-Osias2, Cristy R C Verzijl3
1Oncode Institute, Division of Biochemistry, The Netherlands Cancer Institute, Amsterdam, The Netherlands. g.mclelland@nki.nl.
Nature
|August 30, 2023
まとめ
研究者らは,エネルギーホメオスタシスとミトコンドリア機能に不可欠なタンパク質DIESLとTMX1を含む,ヒトにおけるトライアキルグリセロール (TAG) の合成のための新しい経路を発見した.
科学分野:
- 生物化学
- 細胞生物学
- 代謝の調節
背景:
- トライアキルグリセロール (TAG) は重要なエネルギー貯蔵物ですが,その調節不良は肥満や心臓病と関連しています.
- ダイアシルグリセロールO-アシルトランスフェラーゼ (DGAT1とDGAT2) は,ヒトの TAG 合成の既知の酵素である.
- 人体におけるTAG合成の代替経路の存在は未調査である.
研究 の 目的:
- 人間の細胞でトライアキルグリセロール (TAG) の合成のための潜在的な代替経路を調査する.
- DGAT1とDGAT2を超えてTAGの生物合成に関与する新しい酵素とレギュレータを特定する.
主な方法:
- ヒトのハプロイド細胞における既知のダイアシルグリセロールO-アシルトランスファーゼ (DGAT) 経路の破壊
- 代替TAG合成システムをスクリーニングするために,繰り返し遺伝学を使用します.
- 生物化学的および細胞的測定を用いて,特定されたタンパク質 (DIESLおよびTMX1) の機能を特徴づける.
- ヒトのDIESLをEscherichia coliで発現させ,そのTAG合成能力を確認する.
- マウスモデルでのDIESLの生理学的役割を調査する.
主要な成果:
- 別のTAG合成経路が特定され,アシルトランスファーゼDIESL (TMEM68) とその調節体TMX1が関与した.
- TMX1はエンドプラズマ網膜におけるDIESLの活性を調節し,その欠如は制御不能な脂質滴の形成につながります.
- DIESLは自律的なTAG合成体として機能し,バクテリアでもTAGを合成することができる.
- DIESLは,膜フォスフォリピドを利用してTAGを合成し,栄養素の不足時にミトコンドリア機能をサポートします.
- ネズミのDIESL欠乏は,産後成長とエネルギーバランスを損なう.
結論:
- DIESLによって媒介され,TMX1によって調節される,TAG生物合成のための新しいDGAT独立経路がヒトで発見されました.
- このDIESL主導の経路は,細胞のエネルギー代謝において,特に脂質飢餓の条件下で重要な役割を果たします.
- DIESLはミトコンドリアの機能と全体的なエネルギーホメオスタシスの維持に重要な役割を果たし,代謝疾患にも影響を及ぼします.
関連する概念動画
01:29Biosynthesis of Lipids
35
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
35
01:06Fats as Energy Storage Molecules
25.2K
Triglycerides are a form of long-term energy storage molecules. They are made of glycerol and three fatty acids. To obtain energy from fat, triglycerides must first be broken down by hydrolysis into their two principal components, fatty acids and glycerol. This process, called lipolysis, takes place in the cytoplasm. The resulting fatty acids are oxidized by β-oxidation into acetyl-CoA, which is used by the Krebs cycle. The glycerol that is released from triglycerides after lipolysis...
25.2K
01:25Lipid Catabolism
48
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
48
01:24Overview of Lipid Metabolism
1.7K
Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
1.7K
01:24Other Glycolytic Pathways
44
The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
44
01:28Overview of Fatty Acid Metabolism
30.8K
Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...
30.8K