Nicholls · Biochimica et biophysica acta. Bioenergetics 2021 · narrative review · n=?

Mitochondrial proton leaks and uncoupling proteins.

Cited 135 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of biochemical mechanisms and literature without new empirical human data or systematic synthesis.

PubMed 33798544 · doi:10.1016/j.bbabio.2021.148428 · record verified 2026-08-30

What was done

This narrative review critically examined the 40-year experimental literature on the acute physiological regulation of uncoupling protein 1 (UCP1) in brown adipose tissue by fatty acids, purine nucleotides, and other factors. It evaluated the methodologies used across studies relative to physiological conditions in intact cells, analyzed mechanisms of basal UCP1-independent proton leak, and assessed the evidence surrounding the putative uncoupling functions of UCP2 and UCP3.

What was found

The abstract presents no quantitative data or specific numerical results. It notes that the literature regarding the acute physiological regulation of UCP1 contains extensive and frequently contradictory findings, and it characterizes the research history regarding the uncoupling roles of UCP2 and UCP3 as troubled.

Why it matters

Clarifying how mitochondrial proton leaks and uncoupling proteins are regulated is central to understanding non-shivering thermogenesis and bioenergetic control. Methodological scrutiny helps reconcile conflicting models in the bioenergetics literature.

Limits

The abstract provides no quantitative data or statistical comparisons. As a narrative review, it lacks a systematic search methodology or formal risk-of-bias assessment, relying entirely on mechanistic reasoning and pre-existing laboratory studies.

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