Affiliations: [a] Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [b] Wolfson Centre for Age-Related Diseases, King’s College London, London, UK
| [c] University of Exeter Medical School, University of Exeter, Exeter, UK
Correspondence:
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Correspondence to: Mitchell K.P. Lai, PhD, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Unit 09-01, Centre for Translational Medicine (MD6), 14 Medical Drive, 117599 Singapore. Tel.: +65 6516 8556; Fax: +65 6873 7690; E-mail: mitchell.lai@dementia-research.org.
Abstract: Background:The translocase of the outer membrane (TOM) is a vital mitochondrial transport system facilitating the importation of nuclear encoded proteins into the organelle. While mitochondrial dysfunction, including perturbation of oxidative phosphorylation (OXPHOS) complex, is evident in Alzheimer’s disease (AD), it remains unclear whether the observed OXPHOS deficits may be associated with TOM alterations. Objectives:To correlate TOM subunits with OXPHOS complex proteins in AD. Methods:Postmortem neocortex (BA40) from AD and age-matched controls were processed to obtain mitochondrial enriched homogenates for the measurement of Tom20, Tom22, Tom40, and Tom70 as well as components of OXPHOS complex I–V by immunoblotting. Results:Tom20 and Tom70 immunoreactivities were significantly reduced in AD, as were components of OXPHOS complex I and III. Both Tom20 and Tom70 positively correlated with complex III and V, while Tom20 also correlated withcomplex IV. Conclusion:Reductions in certain TOM subunits and their correlations with specific OXPHOS complex proteins suggest that an impaired mitochondrial transportation system may contribute to previously observed oxidative phosphorylation deficits in AD. Follow-up studies are needed to corroborate the present correlative study.
Keywords: Alzheimer’s disease, mitochondria, oxidative phosphorylation, translocase of the outer membrane
