7q11.23タンパク質DNAJC30はATP合成と相互作用し,ミトコンドリアと脳の発達を結びつける
Andrew T N Tebbenkamp1, Luis Varela2, Jinmyung Choi1
1Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA.
Cell
|October 16, 2018
まとめ
神経発達障害に関連したコピー数変異 (CNV) が研究されている. 研究者らはDNAJC30タンパク質を含むミトコンドリア機能障害が ウィリアムズ症候群の脳欠陥に寄与することを発見しました
科学分野:
- 神経科学
- 遺伝学
- 細胞生物学
背景:
- コピー数変異 (CNV) は神経発達障害の原因として知られています.
- CNV内の遺伝子を神経フェノタイプと結びつける特定のメカニズムはしばしば不明である.
- ウィリアムズ症候群 (WS) は,7q11.23の削除によって引き起こされ,複雑な神経発達上の課題を提示します.
研究 の 目的:
- 神経発達障害における7q11.23 CNVの役割を調査する.
- ウィリアムズ症候群の病原化に寄与する特定の分子機構を特定する.
- WSにおけるミトコンドリア機能の関与を調査する.
主な方法:
- 7q11.23 CNVとその関連タンパク質DNAJC30を研究した.
- ミトコンドリアとニューロンの機能を評価するために,Dnajc30を除去したマウスモデルを使用した.
- ミトコンドリアの酸化リン酸化超複合体の整合性とATP合成ジマー形成をマウスモデルとWS患者サンプルの両方で分析した.
主要な成果:
- ミトコンドリアのATP合成機構と相互作用するタンパク質としてDNAJC30を特定した.
- マウスにおけるDnajc30の除去は,低機能ミトコンドリアと新皮質のピラミッドニューロン形態の障害を引き起こした.
- ミトコンドリア機能障害と一致する,酸化リン酸化超複合体とATP合成ジメルの整合性の低下が観察されました.
結論:
- ミトコンドリア機能障害は ウィリアムズ症候群の病原性における重要な要因である.
- DNAJC30はミトコンドリアのATP合成機構の補助成分である.
- ミトコンドリアの異常は,7q11. 23 CNVに関連した脳の発達と機能の特定の欠陥の基礎である.
さらに関連する動画
15:04Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
6.4K
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
11.8K
関連する概念動画
ATP Synthase: Structure
15.6K
ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
15.6K
ATP Synthase: Mechanism
17.1K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
17.1K
Covalently Linked Protein Regulators
9.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.6K
Covalently Linked Protein Regulators
2.0K
2.0K
ATP Yield
78.9K
Cellular respiration produces 30 - 32 ATP per glucose molecule. Although most of the ATP results from oxidative phosphorylation and the electron transport chain (ETC), 4 ATP are gained beforehand (2 from glycolysis and 2 from the citric acid cycle).
The ETC is embedded in the inner mitochondrial membrane and is comprised of four main protein complexes and an ATP synthase. NADH and FADH2 pass electrons to these complexes, which pump protons into the intermembrane space. This distribution of...
The ETC is embedded in the inner mitochondrial membrane and is comprised of four main protein complexes and an ATP synthase. NADH and FADH2 pass electrons to these complexes, which pump protons into the intermembrane space. This distribution of...
78.9K
Peroxisomes and Mitochondria
95.6K
Peroxisomes and mitochondria are two important oxygen-utilizing organelles in eukaryotic cells. Mitochondria carry out cellular respiration—the process that converts energy from food into ATP. Peroxisomes carry out a variety of functions, primarily breaking down different substances, such as fatty acids.
The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within...
The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within...
95.6K
