プロビチン2はミトコンドリア内膜のミトファジー受容体である
Yongjie Wei1, Wei-Chung Chiang2, Rhea Sumpter2
1Center for Autophagy Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75230, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75230, USA.
Cell
|December 27, 2016
まとめ
この研究では,損傷したミトコンドリアの浄化に不可欠なミトファジー受容体としてプロイビチン2 (PHB2) を特定しました. PHB2は脱極化ミトコンドリアをオートファジー機構と結びつけ,真核生物の保存メカニズムを明らかにする.
科学分野:
- 細胞生物学
- 分子生物学
- オートファギーの研究
背景:
- ミトファギーは 損傷したミトコンドリアをオートファギーを通して 選択的に除去することで 細胞の健康,発達,神経変性などの病気を予防することが重要です
- ミトファギーを制御する正確な分子メカニズムは,まだ完全に理解されていません.
研究 の 目的:
- 新しいミトファジー受容体を特定し,オートファージ分解のためにミトコンドリアをターゲットにする役割を解明する.
- ミトファジー経路におけるプロイビチン2 (PHB2) の機能を調査する.
主な方法:
- ミトファジー受容体としてのPHB2の識別
- ミトコンドリアの脱極化と外膜破裂におけるPHB2とLC3の相互作用の分析.
- 哺乳類の細胞におけるパーキン誘発型ミトファジーとC. elegansにおける父性ミトコンドリアクリアランスのPHB2の必要性の評価
主要な成果:
- Prohibitin 2 (PHB2) は,ミトコンドリア内膜タンパク質であり,ミトファギーの重要な受容体として特定されています.
- PHB2は,LC3相互作用領域 (LIR) を通して,自己ファゴソームタンパク質LC3に直接結合する.
- PHB2は,C. elegansにおけるパーキン媒介型ミトファジーと父性ミトコンドリアクリアランスに不可欠である.
結論:
- PHB2は,自相浄化のために脱極化および損傷したミトコンドリアを標的にする保存受容体として作用する.
- この発見は,老化や病気に影響を及ぼす ユーカリオットミトファギーの重要なメカニズムを明らかにしています
- ミトファジーにおけるPHB2の役割は,その生理学的機能と年齢関連の障害への関与に関する新しい洞察を提供します.
さらに関連する動画
関連する概念動画
Porin Insertion in the Outer Mitochondrial Membrane
5.0K
Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
5.0K
Translocation of Proteins into the Mitochondria
13.6K
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,...
13.6K
Mitochondrial Protein Sorting
5.9K
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...
5.9K
Mitochondrial Precursor Proteins
3.9K
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...
Most of the mitochondrial...
3.9K
Protein Transport into the Inner Mitochondrial Membrane
5.1K
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...
5.1K
Structure of Porins
4.1K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
4.1K


