Related Experiment Video
Updated: Jul 18, 2026
10:00
Use of Enzymatic Biosensors to Quantify Endogenous ATP or H2O2 in the Kidney
Published on: October 12, 2015
Mammalian TOR: a homeostatic ATP sensor
P B Dennis1, A Jaeschke, M Saitoh
1The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
Science (New York, N.Y.)
|November 3, 2001
Summary
Rapamycin, an anticancer drug, targets solid tumors. Researchers found the mammalian Target of Rapamycin (mTOR) pathway senses cellular energy levels (ATP), not just amino acids, impacting cancer growth.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Rapamycin is an effective anticancer agent for solid tumors.
- Solid tumor growth, especially in hypoxia, relies on nutrient and mitogen supply.
- Mammalian Target of Rapamycin (mTOR) regulates ribosome biogenesis and cell growth in response to nutrient availability, particularly amino acids.
Purpose of the Study:
- To investigate the regulatory mechanisms of the mTOR pathway in response to changing nutrient concentrations.
- To determine if the mTOR pathway's regulation is influenced by intracellular ATP levels independently of amino acid abundance.
- To identify mTOR as a direct sensor of cellular ATP concentration.
Main Methods:
- Investigated the influence of intracellular ATP concentration on the mTOR pathway.
- Examined the role of amino acid abundance in mTOR pathway regulation.
- Assessed the direct sensing capabilities of mTOR for ATP.
Main Results:
- The mTOR pathway's activity is modulated by intracellular ATP concentration.
- This ATP-dependent regulation occurs independently of amino acid levels.
- mTOR functions as a direct sensor of intracellular ATP.
Conclusions:
- The mammalian Target of Rapamycin (mTOR) pathway is sensitive to cellular energy status (ATP).
- mTOR acts as an ATP sensor, integrating energy signals into growth regulation.
- This finding provides new insights into cancer metabolism and therapeutic strategies targeting mTOR.
Related Concept Videos
01:27ATP Driven Pumps I: An Overview
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
01:37Energy 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...
03:03mTOR Signaling and Cancer Progression
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
01:34ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
01:30ATP Driven Pumps III: V-type Pumps
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...