Complex I deficiencies in neurological disorders

Sergio Papa; Domenico De Rasmo

doi:10.1016/j.molmed.2012.11.005

Complex I deficiencies in neurological disorders

Trends Mol Med. 2013 Jan;19(1):61-9. doi: 10.1016/j.molmed.2012.11.005. Epub 2012 Dec 19.

Authors

Sergio Papa¹, Domenico De Rasmo

Affiliation

¹ Institute of Biomembranes and Bioenergetics (IBBE), Consiglio Nazionale delle Ricerche, Bari, Italy. sergio.papa@uniba.it

PMID: 23265841
DOI: 10.1016/j.molmed.2012.11.005

Abstract

Complex I is the point of entry in the mitochondrial electron transport chain for NADH reducing equivalents, and it behaves as a regulatable pacemaker of respiratory ATP production in human cells. Defects in complex I are associated with several human neurological disorders, including primary mitochondrial diseases, Parkinson disease (PD), and Down syndrome, and understanding the activity and regulation of complex I may reveal aspects of the underlying pathogenic mechanisms. Complex I is regulated by cyclic AMP (cAMP) and the protein kinase A (PKA) signal transduction pathway, and elucidating the role of the cAMP/PKA system in regulating complex I and oxygen free radical production provides new perspectives for devising therapeutic strategies for neurological diseases.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cyclic AMP / metabolism
Down Syndrome / genetics
Down Syndrome / metabolism
Electron Transport Complex I / deficiency*
Humans
Mitochondrial Diseases / genetics
Mitochondrial Diseases / metabolism
Nervous System Diseases / genetics*
Nervous System Diseases / metabolism*
Oxidative Phosphorylation
Parkinson Disease / genetics
Parkinson Disease / metabolism
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species
Cyclic AMP
Electron Transport Complex I