Hsp70の役割は,ミトコンドリアへのタンパク質転位に単方向性を与えるというものです
C Ungermann1, W Neupert, D M Cyr
1Institut für Physiologische Chemie, Universität München, Germany.
まとめ
ミトコンドリアチャペロンHsp70 (mtHsp70) は,プリプロテインに結合することによって,タンパク質輸入を安定させます. mtHsp70がなければ,タンパク質はミトコンドリアから出ることができ,転位の可逆性を示します.
科学分野:
- ミトコンドリア生物学 ミトコンドリア生物学
- タンパク質の輸入と転移
- 分子チャペロンは,分子チャペローンである.
背景:
- ミトコンドリアは,特定のチャネルとチャペロンを含む複雑なプロセスを通してタンパク質を輸入します.
- タンパク質転位介質の安定化におけるミトコンドリアチャペロンの役割は極めて重要であるが,完全に理解されていない.
研究 の 目的:
- ミトコンドリアチャペロンHsp70 (mtHsp70) が,ミトコンドリアマトリックスへのタンパク質の侵入を促進するメカニズムを調査する.
- 転位介質の安定化におけるmtHsp70の役割と,タンパク質輸入の可逆性を決定する.
主な方法:
- 定義された長さのプレタンパク質がミトコンドリアマトリックスに侵入する過程を研究する.
- mtHsp70が輸入チャネルから発生するタンパク質との相互作用を分析する.
- mtHsp70の結合が転位介質の安定性に与える影響を調査する.
主要な成果:
- ミトコンドリアチャペロンHsp70 (mtHsp70) は,前タンパク質のプレシーケンスの領域と成熟した領域の両方に結合します.
- mtHsp70は,ATPに依存した方法で転位中間物質を安定させます.
- 30-40残留よりも短いプレプロテインは,mtHsp70結合がない場合,ミトコンドリアから拡散し,輸入の可逆性を示すことができます.
結論:
- ミトコンドリアタンパク質の輸入は,シャパロン作用に依存し,遅い段階まで可逆性があります.
- ミトコンドリアのインポートチャネルは,ポリペプチドの相互作用が弱い受動孔として機能します.
- mtHsp70は,ミトコンドリアへの効率的で一方的なタンパク質転位を確保する上で重要な役割を果たしています.
関連する概念動画
Mitochondrial Protein Sorting
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Mitochondrial Precursor Proteins
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Most of the mitochondrial precursors...
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...
Post-translational Translocation of Proteins to the RER
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...


