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Related Concept Videos

Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Non-gated Ion Channels01:24

Non-gated Ion Channels

Ion channels are specialized proteins on the plasma membrane that allow charged ions to pass down their electrochemical gradient. Their main function is to maintain the membrane potential which is critical for cell viability. These channels are either gated or non-gated and can transport more than a thousand ions within milliseconds for the cellular event to occur.
Compared to the gated ion channels, the non-gated channels, also known as leakage or passive channels, have no gating mechanism.
Primary Active Transport01:29

Primary Active Transport

In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would not...
Primary Active Transport01:47

Primary Active Transport

In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps that are embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they...
ATP Driven Pumps II: P-type Pumps01:34

ATP 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...
Single-pass Transmembrane Proteins01:25

Single-pass Transmembrane Proteins

Integral membrane proteins are tightly associated with the cell membrane and play a crucial role in cell communication, signaling, adhesion, and transport of the molecules. Some integral membrane proteins are present only in the membrane monolayer. For example, the enzyme fatty acid amide hydrolase is present in the cytoplasmic side of the membrane monolayer. In contrast, another type of integral membrane protein, also known as a transmembrane protein, spans across the membrane. Transmembrane...

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Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
07:35

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess

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Uncoupling protein-1 is not leaky.

Irina G Shabalina1, Mario Ost, Natasa Petrovic

  • 1The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden.

Biochimica Et Biophysica Acta
|April 20, 2010
PubMed
Summary
This summary is machine-generated.

Uncoupling protein-1 (UCP1) activity, crucial for thermogenesis, is inhibited by nucleotides. Optimal conditions revealed no evidence of residual proton leak in UCP1, even when saturated, refuting prior suggestions.

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Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
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Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

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Area of Science:

  • Mitochondrial bioenergetics
  • Thermogenesis research
  • Brown adipose tissue physiology

Background:

  • Uncoupling protein-1 (UCP1) regulates thermogenesis but its residual activity is debated.
  • Inhibition by GDP and ATP is characteristic, but a persistent proton leak is proposed.
  • Such a leak has implications for weight management via UCP1 overexpression.

Purpose of the Study:

  • To investigate whether UCP1 exhibits residual proton conductance when saturated with inhibitory nucleotides (GDP/ATP).
  • To establish optimal experimental conditions for studying UCP1 bioenergetics in mitochondria.
  • To clarify the functional state of UCP1 under inhibitory conditions.

Main Methods:

  • Comparative bioenergetic analysis of wild-type and UCP1-/- brown fat mitochondria.
  • Optimization of substrate, albumin concentration, and ionic medium composition.
  • Assessment of post-GDP respiration, membrane potential, and proton leak under varying conditions.

Main Results:

  • Optimal conditions identified: pyruvate or palmitoyl-L-carnitine as substrates, 0.1-0.6% albumin, and 125 mM sucrose medium.
  • No evidence of residual proton conductance was found for UCP1 under these optimal conditions.
  • Experimental artifacts under non-optimal conditions can mimic residual UCP1 activity.

Conclusions:

  • UCP1 does not possess a significant residual proton conductance when saturated with GDP/ATP.
  • Optimal experimental conditions are crucial for accurately assessing UCP1 function.
  • Findings align with physiological data indicating UCP1 is non-conductive when inhibited.