ADP/ATPトランスロケータは,ミトコンドリアの透過性の移行孔には不可欠ではありません
Jason E Kokoszka1, Katrina G Waymire, Shawn E Levy
1Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, California 92697, USA.
Nature
|January 30, 2004
まとめ
アデニンヌクレオチドトランスロケータ (ANT) は,アポトーシス中のミトコンドリアの透過性移行孔 (mtPTP) の形成に不可欠ではありません. ANTはmtPTPの活性化を調節しますが,その欠如は細胞死亡シグナリングを防ぐことはありません.
科学分野:
- ミトコンドリア生物学 ミトコンドリア生物学
- 細胞死経路について
- バイオケミストリー バイオケミストリー
背景:
- ミトコンドリアの透過性移行孔 (mtPTP) は,アポトーシスの中心にある.
- アデニンヌクレオチドトランスロケータ (ANT) はmtPTPの構成要素であり,ATPとADPを交換する.
- ANTは,細胞死亡の調節に潜在的に関与しています.
研究 の 目的:
- mtPTPの形成と機能におけるANTの役割を調査する.
- mtPTP媒介によるアポトーシスにおいて,ANTが不可欠であるかどうかを判断する.
主な方法:
- ネズミの肝臓におけるANTイソフォームの遺伝的不活性化.
- 孤立したミトコンドリアにおけるmtPTP活性化の分析.
- ヘパトサイトにおける細胞死誘導の評価.
主要な成果:
- ANTが欠けているミトコンドリアは,それでも透性の移行を経験し,シトクロームcを放出することができる.
- ANT欠乏ミトコンドリアのmtPTP活性化にはCa2+の増加が必要でした.
- ANTリガンドが存在しないと,mtPTPを制御できなくなっていた.
- ANTが欠けている肝細胞は,細胞死誘発剤に反応し続けました.
結論:
- ANTはmtPTPの構造的に欠かせない構成要素である.
- ANTは,mtPTPの活性化と機能の制御的な役割を果たします.
- ANTの欠如は,アポプトシスプロセスを廃止しません.
関連する概念動画
The Inner Mitochondrial Membrane
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
ATP Synthase: Mechanism
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 ATP...
The ADP/ATP Carrier Protein
ADP/ATP carrier or AAC protein is the most abundant carrier protein in the inner mitochondrial membrane. It transports large quantities of ADP and ATP, equivalent to the average human body weight, every day. Among other transporters, ACC protein is one of the best-studied members of the mitochondrial carrier protein family. The ADP/ATP carrier protein comprises two transmembrane helices connected to a loop and a single alpha-helix on the matrix side. It switches between two conformational...
Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...


