細胞のATP需要は,代謝的に異なるミトコンドリアのサブ集団を生み出します
Keun Woo Ryu1, Tak Shun Fung1, Daphne C Baker1
1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|November 7, 2024
まとめ
ミトコンドリアは代謝経路を動的に分離する. 酸化性リン酸化 (OXPHOS) の増加はプロリン合成酵素を隔離し,細胞の成長とバイオエネルギーに影響を与える.
科学分野:
- 細胞生物学
- 生物化学
- ミトコンドリア生物学
背景:
- ミトコンドリアは細胞の成長に不可欠であり,酸化性リン酸化 (OXPHOS) 経由でATPを生産し,還元合成経由で前駆体を作ります.
- プロリンとオルニチンの合成は,OXPHOSとは異なり,ミトコンドリア内の還元経路に依存しています.
- ミトコンドリア内のこれらの競合する代謝経路の空間的組織は不明である.
研究 の 目的:
- ミトコンドリアが競合するOXPHOSと還元合成経路をどのように管理するかを調査する.
- 代謝経路分離におけるミトコンドリアダイナミクスの役割を明らかにする.
主な方法:
- 異なるOXPHOS要求下でピロリン5炭酸塩合成酵素 (P5CS) の局所化を調査した.
- ミトコンドリア融合 (ミトフシン) と分裂 (ダイナミン型タンパク質-1) の遺伝的および薬理学的破壊を活用した.
- ミトコンドリアの構造,CristaeとATP合成酵素の分布,そして代謝出力への影響を評価した.
主要な成果:
- OXPHOSの需要の増加は,CristaeとATP合成体が欠けているミトコンドリアでP5CSの結合につながります.
- P5CSフィラメント形成とミトコンドリアの融合/分裂ダイナミクスは,この分離を推進する.
- ミトコンドリアのダイナミクスを破壊すると,P5CS分離が妨げられ,OXPHOSまたはプロリン合成が損なわれます.
結論:
- ミトコンドリアの分裂と融合は,酸化的および還元的生物合成経路の分離に不可欠である.
- このダイナミックな空間的組織により 細胞は栄養素の供給と需要に基づいて エネルギー生産と前駆体合成のバランスをとることができます
- ミトコンドリアのダイナミクスは,細胞が代謝ストレスに適応する上で重要な役割を果たします.
関連する概念動画
Mitochondria
11.2K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
11.2K
Mitochondrial Membranes
9.0K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
9.0K
Animal Mitochondrial Genetics
7.5K
Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
7.5K
Peroxisomes and Mitochondria
86.6K
Peroxisomes and mitochondria are two important oxygen-utilizing organelles in eukaryotic cells. Mitochondria carry out cellular respiration—the process that converts energy from food into ATP. Peroxisomes carry out a variety of functions, primarily breaking down different substances, such as fatty acids.
The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within...
The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within...
86.6K
Cellular Respiration
1
Cellular respiration is a crucial metabolic process through which cells obtain energy from organic substances, mainly glucose, to produce adenosine triphosphate (ATP). This process includes the oxidation of substrates and the transfer of electrons to a separate electron acceptor, facilitating ATP synthesis through a sequence of biochemical reactions.Glycolysis: The Initial StepGlycolysis is the first stage of cellular respiration, occurring in the cytoplasm of both prokaryotic and eukaryotic...
1
The Inner Mitochondrial Membrane
3.3K
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...
3.3K


