Kinematics or Dynamics?
Why Biologists Missed the Real Engine of Life for 60 Years
By Sungchul Ji, Ph.D.
Professor Emeritus, Theoretical Cell Biology, Rutgers University
(with the assistance of ChatGPT)
1. Introduction: How Mitochondria Power Life
Every living cell depends on a central miracle: the transformation of food energy into ATP—the energy currency of life—catalyzed by mitochondria. For over half a century, the chemiosmotic model of oxidative phosphorylation, proposed by Peter Mitchell in 1961, has been enshrined in every major biochemistry textbook. According to this model, food-derived electrons drive the formation of a proton gradient (PG) across the inner mitochondrial membrane, and ATP is produced as protons flow back into the matrix space through ATP synthase.
This view, though elegant, is incomplete—if not deeply flawed.
2. A Tale of Two Models: Chemiosmosis vs Conformons
A bird’s-eye view of the difference between the chemiosmotic model and the conformon model is given in Table 1. The key mechanistic difference is indicated in the penultimate row of Table 1:
(1) The chemiosmotic model assumes that the only function of mitochondria is to make ATP coupled to respiration.
(2) In contrast, the conformon (defined in the legend to Table 2 below) model assumes that mitochondria carry out dual functions – (i) synthesize ATP only whenever the cell needs it, and (ii) export ATP from the matrix space where it is synthesized into the cytosol whenever it is needed. For this reason, mitochondria utilize respiration-derived energy (i.e., conformons) not only to make ATP but also to produce the proton gradient across the inner membrane as a means of communication with the cytosol.
3. The Chemiosmotic Shortfall
While Peter Mitchell was awarded the 1978 Nobel Prize in Chemistry, the chemiosmotic hypothesis suffers from three fundamental deficiencies:
1. Mechanistic Gap #1: How is the Proton Gradient Formed?
The chemiosmotic model assumes a proton gradient is created by the respiratory chain (see Figure 1 in Table 1) but offers no detailed, enzymologically realistic mechanism for how this occurs at the molecular level.
2. Mechanistic Gap #2: How Does Proton Flow through ATP Synthase Make ATP?
It is further assumed that protons flowing back into the matrix through ATP synthase (see Figure 1 in Table 1) somehow drive the phosphorylation of ADP to ATP. But no quantum-mechanically realistic mechanism has ever been elucidated to show how this coupling occurs.
3. Functional Gap: The chemiosmotic model assumes that the ATP synthesis is the only biological function of mitochondria but recent evidence indicate that mitochondria not only make ATP but also participate in regulating cell metabolism as well [5], most likely through their ability to carry out active transport (see Figure 2 in Table 1).
These are not minor details—they are the core of the problem.
4. A Tale of Two Models: Chemiosmosis (Kinematics/Astrology) vs Conformons (Dyanamics/Astronomy)
It is important to note that physicists distinguish between kinematics and dynamics. Kinematics (https://en.wikipedia.org/wiki/Kinematics) describes the motion of objects in space and time without specifying the cause of motions. Dynamics (https://en.wikipedia.org/wiki/Analytical_dynamics) investigates the motion of bodies and their force-generating mechanisms. The chemiosmotic model is concerned primarily with the ‘kinematics’ of oxidative phosphorylation, i.e., the movement of protons within and across biomembranes without specifying the force-generating mechanism supporting the proton movement (see Figure 1 in Table 1). In contrast, the conformon model is built upon detailed molecular mechanisms underlying the conversion of the chemical energy of oxidizable substrate to the mechanical energy of the ATP synthase that drives the synthesis of ATP from ADP and Pi (see Figure 2 in Table 1). The chemiosmotic model and the conformon model are reproduced in the second row of Table 1. The arrows in the chemiosmotic model in Figure 1 indicate the movement of protons without any driving force behind their movement specified and hence represent kinematics of particle motions. The arrows in the conformon model in Figure 2 indicate not only the movement of particles (i.e., protons and proteins) but also the forces behind their movement, e.g., the exergonic chemical reactions or conformons (symbolized by ~), representing the dynamics of particle motions
5. Why Chemiosmosis Prevailed – and Conformons Were Forgotten for Over Half a Century
There may be at least five reasons:
(1) Argument from Ignorance (Appeal to Ignorance): This fallacy occurs when someone assumes that a proposition is false simply because it has not been definitively proven true (or vice versa). This is an argument from ignorance – the absence of familiar evidence is taken as proof of absence. In reality, the conformon model is supported by indirect evidence and addresses known issues; just because conformons (defined in the legend to Table 2) haven’t been directly visualized or are not part of the mainstream canon does not mean they are nonexistent.
(2) Neglect of Mechanistic Explanation (Incomplete Analysis): A subtler error is the willingness to accept an explanation that lacks mechanistic detail while rejecting one that offers such detail. If a biologist insists on chemiosmosis as the only model but cannot explain how proton pumping actually occurs, they are essentially neglecting the mechanistic explanation. By dismissing conformon theory – which strives to provide a mechanism (e.g., conformational energy transfer) – the scientist is effectively saying, “We prefer to have no mechanism than to consider this alternative mechanism.” Preferring an incomplete theory over a more complete one (simply because the former is familiar) is an intellectual bias. Ignoring the need for a molecular mechanism in favor of a black-box model is a conceptual error – it’s like being content with knowing a car runs without caring to find out that an engine with pistons is what actually makes it run. The conformon model opens the hood of the car, so to speak, and if a biologist slams it shut without looking, they are neglecting critical mechanistic insight.
(3) False Dichotomy (Either-Or Fallacy): Another logical mistake would be framing the situation as chemiosmotic versus conformon as if only one can be true. A biologist might think they must choose loyalty to Mitchell’s model or entertain the conformon model or similar non-chemiosmotic models [8], but not both. This is a false dichotomy. In reality, these models are not mutually exclusive – in fact, they can be viewed as describing different layers of the same process, albeit not in the same detail. The chemiosmotic model describes the thermodynamic outcome (a proton gradient that drives ATP synthase), whereas the conformon model describes a possible mechanism for achieving that outcome (conformational work coupling the reactions). One could easily incorporate conformon concepts into a modernized chemiosmotic framework. By rejecting conformon theory out-of-hand, a scientist might be falsely assuming that accepting it means rejecting the entire chemiosmotic principle. In fact, a more nuanced view is that chemiosmosis and conformational coupling are supplementary: chemiosmosis tells us what the energy intermediate is (protons out, then in), while conformon theory tells us how it might be generated and utilized physically. Treating them as either-or choices is a logical fallacy that oversimplifies the situation. The truth may be a synthesis – i.e., electron transport generates conformons, which both pump protons and directly drive ATP synthase.. Thus, dismissing one in favor of the other could be throwing the baby out with the bathwater.
(4) Appeal to Authority or Consensus: A biologist might also disregard the conformon model simply by noting that “the vast majority of scientists accept the chemiosmotic theory; it’s in all the textbooks; Mitchell got the Nobel Prize for it in 1978; therefore alternative ideas are unnecessary or fringe.” This reasoning is an appeal to authority/popularity. While consensus is an important consideration (especially when a theory is very well-supported), science has plenty of examples where minority viewpoints brought important new insights. The conformon model was proposed by S. Ji (1937 - ) in 1972-4 in collaboration with David E. Green (1927-2018), who was a prominent bioenergeticist in the 1970’s and 80’s. Dismissing it solely because it’s not the current mainstream view is not a scientific argument. The appeal to tradition (“we’ve explained oxphos this way for decades, so why change it?”) also falls in this category. Such an appeal ignores that scientific knowledge is always evolving. Sticking to a theory because it’s established, while ignoring evidence that suggests refinements, is fallacious. It risks fossilizing knowledge instead of advancing it.
(5) Confirmation Bias and Cherry-Picking: If one outright refuses to acknowledge experimental findings that support conformational coupling (such as those described in [2, 8], focusing only on data that fits the classical model, that is an example of confirmation bias. It’s not a formal logical fallacy in argumentation, but it’s a cognitive error in scientific reasoning. A scientist exhibiting this might say, “We know uncouplers stop ATP synthesis by dissipating the proton gradient, therefore chemiosmosis is complete; I will not consider experiments that show anomalies.” This cherry-picks supportive evidence and ignores inconvenient evidence. A robust theoretical analysis should account for all data – both the data explained by chemiosmosis and the data that hint at something more. Ignoring the latter is logically unsound and can lead to fallacious dismissal of a valid model
6. Toward a New Biology: From Description to Explanation.
If biology is to become a predictive science of life—as physics is for matter—then it must graduate from descriptive metaphors to mechanistic rigor. This requires a shift from kinematics (astrology) to dynamics (astronomy) in molecular bioenergetics.
The rediscovery of the conformon model could mark a turning point. With the right theoretical framework, we may finally come to understand how life truly powers itself, from the inside out.
References
[1] Mitchell, P. (1961). Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism. Nature 191, 144–148.
[2] Ji, S. (2025). Chemiosmotic vs Conformon Models of Oxidative Phosphorylation: Theory and Mechanistic Insights. BioSystems (in press).
[3] Ji, S. (2000). Free energy and Information Contents of Conformons in proteins and DNA, BioSystems 54, 107-130.
[4] Green, D.E. and Ji, S. (1972b). Electromechanochemical Model of Mitochondrial Structure and Function. Proc. Nat. Acad. Sci. (U.S.) 69, 726‑- 729.
[5] Waters, H. (2025). Mitochondria: Way More Than ‘Powerhouses’. https://www.linkedin.com/pulse/mitochondria-way-more-than-powerhouses-quanta-magazine-mzrre
[6] Kelso, J.A.S. (2009). Coordination Dynamics. In: Meyers, R. (eds) Encyclopedia of Complexity and Systems Science. Springer, New York, NY. https://doi.org/10.1007/978-0-387-30440-3_1/
[7] Ji, S. (2012). Molecular Theory of the Living Cell: Concepts, Molecular Mechanisms, and Biomedical Applications. Springer, New York. P. 555.
[8] Nath, S. (2025). Rethinking the Classical Chemiosmotic Theory. Biol Theory. https://doi.org/10.1007/s13752-025-00499-3
💬 Comments Welcome
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