PMID- 34085315 OWN - NLM STAT- MEDLINE DCOM- 20220210 LR - 20220210 IS - 1097-4547 (Electronic) IS - 0360-4012 (Linking) VI - 99 IP - 9 DP - 2021 Sep TI - Efficient extra-mitochondrial aerobic ATP synthesis in neuronal membrane systems. PG - 2250-2260 LID - 10.1002/jnr.24865 [doi] AB - The nervous system displays high energy consumption, apparently not fulfilled by mitochondria, which are underrepresented therein. The oxidative phosphorylation (OxPhos) activity, a mitochondrial process that aerobically provides ATP, has also been reported also in the myelin sheath and the rod outer segment (OS) disks. Thus, commonalities and differences between the extra-mitochondrial and mitochondrial aerobic metabolism were evaluated in bovine isolated myelin (IM), rod OS, and mitochondria-enriched fractions (MIT). The subcellular fraction quality and the absence of contamination fractions have been estimated by western blot analysis. Oxygen consumption and ATP synthesis were stimulated by conventional (pyruvate + malate or succinate) and unconventional (NADH) substrates, observing that oxygen consumption and ATP synthesis by IM and rod OS are more efficient than by MIT, in the presence of both kinds of respiratory substrates. Mitochondria did not utilize NADH as a respiring substrate. When ATP synthesis by either sample was assayed in the presence of 10-100 microM ATP in the assay medium, only in IM and OS it was not inhibited, suggesting that the ATP exportation by the mitochondria is limited by extravesicular ATP concentration. Interestingly, IM and OS but not mitochondria appear able to synthesize ATP at a later time with respect to exposure to respiratory substrates, supporting the hypothesis that the proton gradient produced by the electron transport chain is buffered by membrane phospholipids. The putative transfer mode of the OxPhos molecular machinery from mitochondria to the extra-mitochondrial structures is also discussed, opening new perspectives in the field of neurophysiology. CI - (c) 2021 Wiley Periodicals LLC. FAU - Ravera, Silvia AU - Ravera S AUID- ORCID: 0000-0002-0803-1042 AD - Department of Experimental Medicine, University of Genoa, Genoa, Italy. FAU - Bartolucci, Martina AU - Bartolucci M AUID- ORCID: 0000-0001-5289-4219 AD - Laboratory of Mass Spectrometry - Core Facilities, Istituto Giannina Gaslini, Genoa, Italy. AD - Department of Pharmacy, Biochemistry Lab., University of Genoa, Genoa, Italy. FAU - Calzia, Daniela AU - Calzia D AD - Department of Pharmacy, Biochemistry Lab., University of Genoa, Genoa, Italy. FAU - Morelli, Alessandro M AU - Morelli AM AD - Department of Pharmacy, Biochemistry Lab., University of Genoa, Genoa, Italy. FAU - Panfoli, Isabella AU - Panfoli I AUID- ORCID: 0000-0002-6261-1128 AD - Department of Pharmacy, Biochemistry Lab., University of Genoa, Genoa, Italy. LA - eng PT - Journal Article DEP - 20210603 PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/administration & dosage/*biosynthesis MH - Animals MH - Cattle MH - Cell Membrane/drug effects/*metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Male MH - Mitochondria/drug effects/*metabolism MH - Neurons/drug effects/*metabolism MH - Oxygen Consumption/drug effects/physiology MH - Prosencephalon/drug effects/*metabolism MH - Retina/drug effects/*metabolism OTO - NOTNLM OT - RRID:AB_10696805 OT - RRID:AB_11183050 OT - RRID:AB_1845182 OT - RRID:AB_2818988 OT - RRID:AB_2851910 OT - RRID:SCR_002798 OT - RRID:SCR_014210 OT - aerobic metabolism OT - bioenergetics OT - myelin sheath OT - oxidative phosphorylation OT - phototransduction OT - rod outer segments disks EDAT- 2021/06/05 06:00 MHDA- 2022/02/11 06:00 CRDT- 2021/06/04 07:24 PHST- 2021/04/29 00:00 [revised] PHST- 2020/05/13 00:00 [received] PHST- 2021/05/10 00:00 [accepted] PHST- 2021/06/05 06:00 [pubmed] PHST- 2022/02/11 06:00 [medline] PHST- 2021/06/04 07:24 [entrez] AID - 10.1002/jnr.24865 [doi] PST - ppublish SO - J Neurosci Res. 2021 Sep;99(9):2250-2260. doi: 10.1002/jnr.24865. Epub 2021 Jun 3.