The aerobic mitochondrial ATP synthesis from a comprehensive point of view

Abstract

Most of the ATP to satisfy the energetic demands of the cell is produced by the F₁F_o-ATP synthase (ATP synthase) which can also function outside the mitochondria. Active oxidative phosphorylation (OxPhos) was shown to operate in the photoreceptor outer segment, myelin sheath, exosomes, microvesicles, cell plasma membranes and platelets. The mitochondria would possess the exclusive ability to assemble the OxPhos molecular machinery so to share it with the endoplasmic reticulum (ER) and eventually export the ability to aerobically synthesize ATP in true extra-mitochondrial districts. The ER lipid rafts expressing OxPhos components is indicative of the close contact of the two organelles, bearing different evolutionary origins, to maximize the OxPhos efficiency, exiting in molecular transfer from the mitochondria to the ER. This implies that its malfunctioning could trigger a generalized oxidative stress. This is consistent with the most recent interpretations of the evolutionary symbiotic process whose necessary prerequisite appears to be the presence of the internal membrane system inside the eukaryote precursor, of probable archaeal origin allowing the engulfing of the α-proteobacterial precursor of mitochondria. The process of OxPhos in myelin is here studied in depth. A model is provided contemplating the biface arrangement of the nanomotor ATP synthase in the myelin sheath.

Keywords: ATP synthase; endoplasmic reticulum; extra-mitochondrial; mitochondria; myelin; oxidative phosphorylation.

Figure 1.

Updated possible mitochondria evolution: the archaea, which displayed a development of internal membranes, engulfed the bacterium expressing the OxPhos machinery, coming in contact with the inner membranes of the archaea. There is a reciprocal remodelling (the inner membranes achieve the OxPhos machinery) and the bacterium acquires from the archaea the molecular devices (small molecular weight-G-protein in primis) that determine remodelling and the bacterium forms the cristae, rendering the aerobic ATP synthesis more efficient. The symbiosis with bacteria generates the nucleus in the archaea [28].

Figure 2.

Schematic of macromolecular membrane pumps binding ATP (a) and respiratory complex I binding NADH (b), embedded in the membrane. The protective layer of water adhering to the membrane and the protrusion for about 10 nm of the zone with low dielectric constant are indicated.

Figure 3.

Schematic of a bi-faced ATP synthase arrangement in myelin, sustaining proton currents delivered by respiratory complex I, establishing a proton circuit entirely built inside a major dense line of myelin.