A major challenge in biomedical science is ATP supply in the nervous system (NS). The mitochondrial Electron Transfer Chain (ETC), Fo F1 -ATP synthase and Tricarboxylic Acid (TCA) Cycle enzymes are functionally expressed outside the mitochondrion, in myelin and rod outer segments (OS). These extra-mitochondrial sites of oxidative phosphorylation (OXPHOS), devoid of mitochondria, consume oxygen (O2 ) and synthesize ATP in the presence of any TCA Cycle intermediate, in a manner sensitive to mitochondrial probes and inhibitors. During rat myelinogenesis expression of myelin basic protein, ETC, Fo F1 - ATP synthase and mitochondrial fusion proteins increased from day 0 to 33, while that of inner mitochondrial membrane proteins decreased. Exosomes from various sources conduct an extra-mitochondrial OXPHOS, suggesting a protein transfer from mitochondria to the endoplasmic reticulum. The OXPHOS is a major source of reactive O2 species in the rod OS, that polyphenols can scavenge, by inhibiting the ectopic Fo F1 -ATP synthase. Oxidative stress originated by the extramitochondrial OXPHOS may represent a pivotal pathogenic mechanism for many neurodegenerative diseases.

Pathophysiology of the extra-mitochondrial oxidative phosphorylation

Isabella Panfoli
2016

Abstract

A major challenge in biomedical science is ATP supply in the nervous system (NS). The mitochondrial Electron Transfer Chain (ETC), Fo F1 -ATP synthase and Tricarboxylic Acid (TCA) Cycle enzymes are functionally expressed outside the mitochondrion, in myelin and rod outer segments (OS). These extra-mitochondrial sites of oxidative phosphorylation (OXPHOS), devoid of mitochondria, consume oxygen (O2 ) and synthesize ATP in the presence of any TCA Cycle intermediate, in a manner sensitive to mitochondrial probes and inhibitors. During rat myelinogenesis expression of myelin basic protein, ETC, Fo F1 - ATP synthase and mitochondrial fusion proteins increased from day 0 to 33, while that of inner mitochondrial membrane proteins decreased. Exosomes from various sources conduct an extra-mitochondrial OXPHOS, suggesting a protein transfer from mitochondria to the endoplasmic reticulum. The OXPHOS is a major source of reactive O2 species in the rod OS, that polyphenols can scavenge, by inhibiting the ectopic Fo F1 -ATP synthase. Oxidative stress originated by the extramitochondrial OXPHOS may represent a pivotal pathogenic mechanism for many neurodegenerative diseases.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/892408
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