Beyond Mitochondrial Dysfunction: Why Energy Flow Matters More Than the Machinery

Every living cell is powered by a complex network of reactions that turn nutrients into usable energy. In their recent paper, Energy Metabolism in Health and Diseases, Liu and colleagues deliver an impressive tour through this landscape—showing how energy pathways such as glycolysis, fatty-acid oxidation, and mitochondrial respiration underpin health and, when disrupted, drive disease.

The review’s strength lies in its mechanistic depth. It traces how mitochondrial damage, oxidative stress, and altered fuel use connect to cancer, neurodegeneration, and heart disease. It also highlights exciting frontiers—multi-omics mapping of metabolism, organoid models, and even therapeutic mitochondrial transfer. For anyone studying the “engine room” of life, it’s an essential read.

Yet, as with many mechanistic reviews, the story flows in only one direction:

mitochondrial dysfunction → disease.

What’s missing is the equally important question:

What causes the dysfunction in the first place?

🧩 The Missing Half of the Picture

Mitochondria don’t fail in isolation. They falter when their nutrient networks and adaptive rhythms are chronically disturbed.

• Nutrient network availability: Vitamins, amino acids, and minerals act as cofactors for every mitochondrial enzyme. Even mild insufficiency can slow the metabolic “assembly line.”

• Rhythm of catabolism and anabolism: Healthy physiology alternates between breakdown (to free energy) and rebuilding (to restore tissues). Chronic stress, overwork, inflammation, or sleep loss trap the body in a catabolic loop—burning without repair.

• Systemic regulation: Hormones, immune signals, and neural inputs coordinate when mitochondria accelerate or conserve energy. Persistent stress can mis-signal these controls, forcing the system into exhaustion.

When these upstream layers break down, mitochondria are simply the first responders that run out of fuel.

🌍 The ERM Perspective

The Exposure-Related Malnutrition (ERM) framework expands this view. It treats bioenergetic breakdown not as an isolated cellular accident but as the cumulative outcome of exposure, adaptation, and depletion.

• Early exposure (psychological, inflammatory, or environmental) triggers adaptive stress responses.

• Over time, nutrients and redox capacity become misallocated.

• Eventually, energy can no longer flow where it’s needed most—leading to “malnutrition from within.”

From this perspective, mitochondrial dysfunction is a symptom of energy misallocation, not merely the root cause.

The cure is not only to repair mitochondria but to restore the rhythm of energy availability, allocation, and recovery.

🧭 A Broader Way Forward

The future of metabolic health research must join both views:

1. The mechanistic precision of Liu et al.—understanding the biochemical gears.

2. The systemic ecology of ERM—how lifestyle, stress, and nutrient patterns keep those gears turning smoothly.

Energy metabolism is not just chemistry; it’s choreography.

And health is the music that plays when every cell still remembers the rhythm.

Reference:

Liu X, et al. (2025). Energy Metabolism in Health and Diseases. Signal Transduction and Targeted Therapy.