In defense of the murburn explanation for aerobic respiration

Abstract

The murburn explanation for aerobic respiration was first published at Biomedical Reviews in 2017. Thereafter, via various analytical, theoretical and experimental arguments/evidence published in respected portals over the last three years, my group's works had highlighted the untenable nature of the "electron transport chain (ETC)-driven chemiosmotic rotary ATP synthesis (CRAS)" explicatory paradigm for aerobic respiration. We have also presented strong evidence and arguments supporting the new murburn model of mitochondrial oxidative phosphorylation (mOxPhos). Overlooking the vast majority of our critical dissections, CRAS hypothesis is still advocated by some. Further, queries are posed on the evidence-based murburn explanation without any committed effort to understand the new proposals. Herein, I expose the false attributions made to our works, point out the general and particular flaws/lacunae in the critical attention murburn model received, revisit/dissect the arguments critique(s) floated to support the chemiosmotic proposal, answer the specific queries on murburn explanation and defend/consolidate our proposals for mOxPhos. The current scientific discourse is crucial for correcting major historical errors and finding/founding new concepts of the powering logic and biophysical chemistry of life.

Why do cells need oxygen? Insights from mitochondrial composition and function

“…In his recent manuscripts published in Biophysical Chemistry , Sunil Nath (advocate of TITAS) dismisses Silva's defense of the CRAS proposal (Nath, 2021a, 2021b). Nath is sure that Mitchell's erroneous assumptions of a one‐ion (i.e., only proton) current destroy the chemiosmosis proposal, and this should be corrected by his “two‐ion hypothesis.” Nath and Silva also insinuate that Manoj misunderstands CRAS‐TITAS (Nath, 2020; Silva, 2020), which we believe does not stand in merit with respect to our point‐wise criticisms and rebuttals (Manoj, Parashar, et al, 2019; Manoj, Soman, et al, 2019; Manoj, 2020a, 2020b, 2020c). A resolution of this conflict cannot be derived without inspecting the founding principles of the proposals.…”

“…Before this was mooted, the more popular perception was that of Edward Slater's energetic phosphorylations being mediated by a high-energy enzymic catalytic intermediate (Slater, 1953), which was seconded by Paul Boyer's proposal of phosphohistidine (Boyer, 1963). Several seasoned researchers -practically, the who's who of biochemistry-physiology research in mid-20th century, to name a few: Britton Chance, Gilbert Ling, David Green, Robert Williams, Albert Lehninger, Gregorio Weber, Edward Slater, Walter Wainio, and so on, vehemently opposed Mitchell's idea (Manoj, 2020a). Despite this, the chemiosmotic theory gained traction and won the "OxPhos war" within the next two decades.…”

“…Over the last two decades, Sunil Nath had questioned some aspects of the CRAS proposal, more precisely its violation of the law of electro-neutrality, and made alterations to classical roles of Complex V and ions within the reaction scheme, and continues to advocate his framework as "two-ion torsional ATP synthesis" (abbreviated herein as TITAS; Nath, 2017). As of today, although a clear mechanistic consensus is lacking among the various schools' advocates and critics (Lee, 2019;Manoj, 2020aManoj, , 2020bManoj, , 2020cNath, 2021aNath, , 2021bSilva, 2020Silva, , 2021, the vast majority of data in bioenergetics/biological research continues to be interpreted within the CRAS paradigm, and students are taught this paradigm at schools and universities across the globe.…”

Murburn concept: A tangible bioenergetic rationale for the origin, sustenance, termination, and evolution of life

“…It is easy to see that this logic can be operational across the diverse habitats. Through my writings, I have left not minced words and have repeatedly pointed out that chemiosmosis is an 'irreducibly complex' (anti-evolution term coined by Michael Behe) and thermodynamically invalid proposal and thus, inherently nonevolvable (Manoj, 2020)! It can be seen that half a century's pursuit with this idea has not led us to any meaningful understanding of life; not even a consensus among its advocates (Manoj, 2020; as can be noted from the accompanying supplementary information file).…”

“…Through my writings, I have left not minced words and have repeatedly pointed out that chemiosmosis is an 'irreducibly complex' (anti-evolution term coined by Michael Behe) and thermodynamically invalid proposal and thus, inherently nonevolvable (Manoj, 2020)! It can be seen that half a century's pursuit with this idea has not led us to any meaningful understanding of life; not even a consensus among its advocates (Manoj, 2020; as can be noted from the accompanying supplementary information file). Therefore, biologists that consider molecular evolution as an acceptable concept of life would consider it opportune to step out of the chemiosmosis paradigm to seek for better bioenergetic principles.…”