ミトコンドリアのピルーバートベアの識別と機能的発現
Sébastien Herzig1, Etienne Raemy, Sylvie Montessuit
1Department of Cell Biology, University of Geneva, Geneva, Switzerland.
まとめ
研究者らは,ピルバ酸塩を mitochondrial pyruvate carrier (MPC) の分子同一性を特定し,これは細胞エネルギー生産のためにピルバ酸塩を mitochondria に輸送するために不可欠な重要なタンパク質複合体である.
科学分野:
- ミトコンドリア生物学 ミトコンドリア生物学
- 分子遺伝学 分子遺伝学
- 細胞の代謝は細胞の代謝である.
背景:
- ミトコンドリアへのピルベート輸送は,細胞呼吸に不可欠です.
- ミトコンドリアのピルーバートキャリア (MPC) の分子的アイデンティティは不明のままでした.
- 以前の研究では,ミトコンドリアのピルベート吸収のための特定のキャリアを予想していました.
研究 の 目的:
- ミトコンドリアのピルバートキャリア (MPC) の分子成分を特定する.
- ピルバート輸送におけるこれまで特徴づけられなかった膜タンパク質の機能を明らかにする.
主な方法:
- ピルバートの吸収を研究するための酵母遺伝学.
- MPCファミリータンパク質の局所化研究.
- 輸送活動を評価するために,Lactococcus lactisにおける異質表現.
主要な成果:
- 2つの新しい膜タンパク質のヘテロ複合体をMPCとして特定しました.
- MPCファミリータンパク質は,ミトコンドリア内膜に位置しています.
- MPCタンパク質が欠けている酵母変異体は,ミトコンドリアのピルバート吸収が低下しています.
- MPC1とMPC2の同時発現により,ピルバートの膜間輸送が容易になりました.
結論:
- ミトコンドリアのピルーバートキャリア (MPC) をMPC1とMPC2のヘテロ複合体として特定した.
- これらのタンパク質は,ミトコンドリアのピルバート輸送と細胞のエネルギー代謝に不可欠です.
- この発見は,ミトコンドリアの燃料供給を理解するための分子基盤を提供します.
関連する概念動画
Pyruvate Oxidation
After glycolysis, the charged pyruvate molecules enter the mitochondria via active transport and undergo three enzymatic reactions. These reactions ensure that pyruvate can enter the next metabolic pathway so that energy stored in the pyruvate molecules can be harnessed by the cells.
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
First, the enzyme pyruvate dehydrogenase removes the carboxyl group from pyruvate and releases it as carbon dioxide. The stripped molecule is then oxidized and releases electrons, which are then picked up by NAD+...
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...
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...
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...
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,...
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...


