Beyond the Chemiosmotic Model: Why It's Time to Embrace the Conformon Theory of ATP Synthesis

Transition from Astrology (Kinematics) to Astronomy (Dynamics)

By Dr. Sungchul Ji
Emeritus Professor of Theoretical Cell Biology
Rutgers University

What fuels life? Nearly every cell in your body depends on a molecule called ATP (adenosine triphosphate)—the energy currency of life. ATP powers everything from muscle contractions to thought processes. But how exactly does your body make ATP from the food you eat?

Since 1961, biology textbooks have answered this question with the chemiosmotic model proposed by Peter Mitchell, for which he was awarded the Nobel Prize in Chemistry in 1978. According to this model, the energy from food is used to pump protons across the mitochondrial membrane, generating a gradient (a "proton motive force") that drives ATP synthesis like water flowing through a turbine.

It’s an elegant metaphor. But it’s also incomplete.

Despite its widespread acceptance, the chemiosmotic model remains fundamentally kinematic—it describes what happens but not how it happens at the molecular level. It fails to account for the detailed mechanical processes inside the ATP synthase enzyme complex, which transforms the mechanical energy of the rotational motion of its γ subunit into the chemical energy of ATP.

In contrast, a little-known alternative, the conformon model—originally proposed in the early 1970s by David E. Green (1910-1983) and myself—offers a dynamically complete, quantum-mechanically realistic, and enzymologically grounded mechanism for how the chemical energy of food is converted into the mechanical motion of the γ subunit, and finally into ATP.

A conformon is a mechanically deformed, metastable conformational state of a biopolymer (like a protein or enzyme). In the conformon model:

1. Chemical energy (from electron transfer in the respiratory chain) is first converted into mechanical energy by deforming segments of respiratory enzymes.
2. These mechanical deformations—conformons—then propagate like localized energy packets.
3. The motion of these conformons powers the rotation of the enzyme’s catalytic machinery, including the γ subunit of ATP synthase leading to ATP synthesis from ADP and Pi.

Unlike the chemiosmotic model, the conformon model provides both the kinematics (the overall steps) and the dynamics (the specific forces and motions) of ATP production.

Why has the conformon model been overlooked?

- Simplicity Bias: The chemiosmotic model is visually easier to depict in diagrams and animations. In contrast, the conformon model requires understanding of more advanced concepts in quantum mechanics, conformational dynamics, and enzymology.
- Authority Bias: The Nobel Prize recognition of Mitchell's work has led many biologists to assume the chemiosmotic model is definitive.
- Lack of Theoretical Training: Many biologists are not trained to evaluate the mechanistic completeness of models.

Ease of depiction is not a substitute for accuracy. And as experimental evidence accumulates, the chemiosmotic model is struggling to account for all observations.

As outlined in Section 2 of the manuscript [1], multiple lines of evidence now challenge the sufficiency of the chemiosmotic theory:

- Local coupling of reactions that cannot be explained by simple diffusion-based proton gradients.
- Observations of ATP synthesis in the absence of measurable proton gradients.
- The inability to account for mechanical conformational changes observed in single-molecule studies of ATP synthase.

These findings support the conformon model, which naturally predicts local energy storage, direct conformational work, and quantized energy transfer consistent with the Generalized Franck–Condon Principle [1].

Why does this matter? Because mitochondria are not just ATP factories—they are central to aging, cancer, neurodegeneration, and metabolism. If our core model of mitochondrial energy production is flawed or incomplete, therapeutic interventions based on it may be suboptimal or misguided.

By integrating the conformon mechanism into biomedical education and research, we may unlock more precise diagnostics, better-targeted drugs, and a more realistic understanding of how life generates, stores, and uses energy.

We do not need to throw out the chemiosmotic model. But we must supplement it with a more complete, dynamic, and mechanistically rigorous framework—the conformon model. It’s time for textbook writers, curriculum developers, and biomedical researchers to update our collective understanding of how life works.

Because understanding life at its most fundamental level—how it moves, transforms, and thrives—depends on getting the mechanism right.

Figure 1. Comparison of Chemiosmotic Model vs. Conformon Model

References:

[1] Ji, S. (2025). Chemiosmotic vs Conformon Models of Oxidative Phosphorylation: Theory and Mechanistic Insights. BioSytems (submitted).