Alternative Splicing and Nonsense Mediated Decay in Mitochondrial Complex-I Biogenesis and its Implication in Human Diseases

Damiano Panelli Francesca,Paola Lorusso Francesco Papa

doi:10.4172/1948-593x.s3-006

Abstract

In mammals, complex-I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain has 31 supernumerary subunits in addition to the 14 conserved from prokaryotes to humans. Multiplicity of structural protein components, as well as of biogenesis factors, make complex-I a sensible pace-maker of mitochondrial respiration. The work reviewed here shows that the Alternative Splicing and Nonsense Mediated Decay pathways regulate the transcription products of different nuclear genes encoding subunits of complex I. Complex-I dysfunction has been found to be associated with several human diseases. Involvement of altered pattern of transcription products of complex-I genes in pathogenetic mechanisms of these diseases is examined.

Highlights

Complex-I is the first enzyme of the mitochondrial respiratory chain
In other cases as for example the Ndufs4 gene [28], and the Ndufb11 gene [30] the alternative splicing transcripts identified could have a role in the regulation of the complex-I biogenesis and their altered expression could be involved in the pathogenetic mechanism of diseases associated with complex-I defect
Since rotenone treatment in the SH-SY5Y cells down-regulates the expression of the hnRNPH1 protein it is likely that the rotenone induced shift in the ratio of the short vs. the long Ndufb11 isoforms, is associated with the depressed capacity of hnRNPH1 to regulate the alternative splicing of the gene

Summary

Introduction

Complex-I is the first enzyme of the mitochondrial respiratory chain. The enzyme catalyzes the transfer of electrons from NADH to ubiquinone [1] in the inner mitochondrial membrane and conserves the free energy, so made available, as a transmembrane electrochemical proton gradient (∆μH+) which is utilized to make ATP from ADP in the mitochondrial process of oxidative phosphorylation (OXPHOS) [2]. In other cases as for example the Ndufs4 gene [28], and the Ndufb11 gene [30] the alternative splicing transcripts identified could have a role in the regulation of the complex-I biogenesis and their altered expression could be involved in the pathogenetic mechanism of diseases associated with complex-I defect.

Results

Conclusion