ゴルギ系PI(4) Pを含む膀はミトコンドリア分裂の遅い段階を駆動する
Shun Nagashima1, Luis-Carlos Tábara1, Lisa Tilokani1
1Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
まとめ
ゴルギの膀におけるフォスファチチドリノシトール4'-フォスファート (PI(4) は,ダイナミン関連タンパク質-1 (Drp1) の下流でミトコンドリアの分裂を誘導する. Arf1またはPI(4) KIIIβの喪失はPI(4) P生成を阻害し,ミトコンドリアネットワークの欠陥を引き起こす.
科学分野:
- 細胞生物学
- 分子生物学
- 生物化学
背景:
- ミトコンドリアの分裂によって制御されるミトコンドリアの可塑性は 細胞の運命を決定します
- ダイナミン関連タンパク質-1 (Drp1) は,内プラズマ網膜 (ER) の接触部位でミトコンドリア分裂を媒介するが,最終的な分裂メカニズムは不明である.
研究 の 目的:
- ミトコンドリア分裂の最終段階を制御する分子メカニズムを解明する.
- ミトコンドリア分裂におけるフォスファチチドリノシトール4リン酸 (PI(4) P) の役割を調査する.
主な方法:
- ミトコンドリアの分裂を研究するために哺乳類の細胞系を使用した.
- ADPリボシライゼーション因子1 (Arf1) とフォスファディチルイノシトール4-キナーゼIIIβ (PI(4) KIIIβ) のPI(4) P生成における機能を調査した.
- 顕微鏡を用いてミトコンドリアの形状と収縮部位を観察した.
主要な成果:
- トランス・ゴルギ・ネットワーク (TGN) のPI(4) PのマイクロドメインはミトコンドリアとERの接触部位に集められた.
- PI(4) Pを含む小胞の徴集は,Drp1のダウンストリームでミトコンドリアの分裂を促した.
- Arf1またはPI(4) KIIIβの喪失はPI(4) P生成を廃止し,ハイパーフューズされたミトコンドリアネットワークと拡張した収縮部位を生成した.
結論:
- TGN-PI ((4) P膀は,ミトコンドリア分裂の最終的なイベントを誘発する上で重要な役割を果たします.
- Arf1-PI ((4) KIIIβ-PI ((4) P経路は,ER接触部位におけるミトコンドリア分裂を調節するために不可欠である.
関連する概念動画
Mitochondrial Protein Sorting
5.5K
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...
5.5K
Translocation of Proteins into the Mitochondria
11.7K
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,...
11.7K
Protein Transport into the Inner Mitochondrial Membrane
4.7K
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...
4.7K
Porin Insertion in the Outer Mitochondrial Membrane
4.3K
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...
4.3K
Distribution of Cytoplasmic Content
4.5K
Cytokinesis segregates a cell’s chromosomes and organelles into its daughter cells. Organelles divide and grow prior to cell division but cannot be synthesized de novo; therefore, cells must receive at least one copy of each organelle to survive. Currently, many of the details of how the organelles are distributed are not yet fully elucidated.
Distribution of cytoplasmic determinants
The cytoplasm contains various organelles, as well as salts, proteins, and water. The distribution of...
Distribution of cytoplasmic determinants
The cytoplasm contains various organelles, as well as salts, proteins, and water. The distribution of...
4.5K
Transport Across the Golgi
5.7K
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
5.7K


