George A. Brooks · Experimental & Molecular Medicine 2022 · narrative review · n=?

Tracing the lactate shuttle to the mitochondrial reticulum

Cited 99 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and mechanistic framework summarizing prior tracer studies without new primary human data

OpenAlex W4295083465 · doi:10.1038/s12276-022-00802-3 · record verified 2026-08-30

What was done

This is a narrative review synthesizing physiological evidence from isotope tracer infusion studies (using lactate, glucose, glycerol, and fatty acid tracers), tissue metabolite concentration assays, and arterial-venous difference (a-v) measurements combined with blood flow determinations across skeletal muscle, heart, and brain tissue beds across various states (rest, exercise, endurance training, sea level, high altitude).

What was found

The abstract reports no quantitative numbers or statistical effect sizes. It summarizes qualitative physiological observations: organ-organ, cell-cell, and intracellular lactate shuttles operate continuously to exchange fuel between producer cells (e.g., skeletal muscle) and consumer cells (e.g., brain, heart, liver, kidneys), between white and red muscle fibers, between astrocytes and neurons, and between the cytosol and mitochondria or peroxisomes, driven by mitochondrial oxidative concentration gradients.

Why it matters

It provides a consolidated mechanistic framework showing that lactate functions as a dynamic, continuously utilized energy substrate linking glycolysis directly to mitochondrial respiration across multiple organ systems.

Limits

The abstract provides no primary data, sample sizes, or numerical measurements. As a narrative synthesis rather than a systematic review, it does not include search criteria, study selection parameters, or risk-of-bias evaluation.

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