What is it about?

An experiment was performed on mice groups incubated at three different temperatures (30, 23, and 6 Celsius degree). The proteome analysis revealed differential expression of proteins leading to discovery/activation of a novel cycle at lower temperature termed HEAT Cycle.

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Why is it important?

It is expected that the newly discovered HEAT Cycle may open new horizons to study mitochondria-related diseases. It will also help in designing futuristic food items. The HEAT Cycle is essentially a pseudo-futile cycle of fatty acid β-oxidation. Its proposed mechanism involves the continuous activation and de-activation of fatty acids within the mitochondria. Fatty acids are first activated by Acyl-CoA synthetases (ACSL1, ACSL5, ACSL6) to form Acyl-CoAs, which then enter the β-oxidation pathway. The central feature of the cycle is the de-activation of these Acyl-CoAs by the enzyme Acyl-CoA thioesterase 11 (ACOT11), releasing the fatty acid. This fatty acid is then immediately re-activated by Acyl-CoA synthetase family member 2 (ACSF2) to re-enter the cycle. The repeated consumption of ATP during the re-activation step, without the full breakdown of the fatty acid for energy, results in the net release of energy as heat. This specialized mechanism highlights a dedicated pathway for heat production in brown adipocytes, distinct from the uncoupling protein UCP1, and represents a significant potential pathway in cellular thermogenesis.

Perspectives

The HEAT Cycle is a proposed metabolic pseudo-futile cycle that occurs in the mitochondria of brown adipose tissue (BAT) and is essential for non-shivering thermogenesis. According to it, heat is generated through uncoupling protein 1 (UCP1), which uncouples protons from the electron transport chain (ETC). The primary fuel used in this process is Acetyl Coenzyme A (Acetyl-CoA). Acetyl-CoA enters the Krebs cycle, producing NADH and FADH2. These molecules then enter the electron transport chain to generate ATP. In cold-acclimated environments, instead of allowing protons from NADH and FADH2 to produce ATP, UCP1 uncouples these protons, resulting in heat production. The Acetyl-CoA is then recycled using NADPH and ATP, making it available for reuse. The discovery emerged from comparative proteomics analysis of mitochondria from the brown fat of mice acclimated to different temperatures (30°C, 23°C, and 6°C).

Dr. Ahmed Hammad Mirza
COMSATS University Islamabad - Sahiwal Campus

Read the Original

This page is a summary of: Comparative proteomics reveals that lipid droplet-anchored mitochondria are more sensitive to cold in brown adipocytes, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, October 2021, Elsevier,
DOI: 10.1016/j.bbalip.2021.158992.
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