Cellular and Molecular Life Sciences

, Volume 68, Issue 24, pp 3963–3969

Age-related lysosomal dysfunction: an unrecognized roadblock for cobalamin trafficking?

Visions and reflections

DOI: 10.1007/s00018-011-0861-9

Cite this article as:
Zhao, H., Brunk, U.T. & Garner, B. Cell. Mol. Life Sci. (2011) 68: 3963. doi:10.1007/s00018-011-0861-9

Abstract

Vitamin-B12 is a generic term for corrinoid compounds that exhibit the biological activity of cyanocobalamin and are collectively referred to as cobalamins. Methylcobalamin and 5-deoxyadenosylcobalamin are the active cobalamins in human metabolism. Cobalamin plays a crucial role in the maintenance of homocysteine and methylmalonyl-CoA homeostasis and is required for erythrocyte formation and DNA synthesis. Data from human and animal studies indicate that cobalamin deficiency impairs neuronal function; a process that is thought to contribute to age-related cognitive decline and dementia. Cobalamin deficiency also results in dysfunction of the peripheral nervous system; among other disorders. Although there is a detailed understanding of the biochemical pathways that are perturbed in cobalamin deficiency, the mechanisms underlying age-related dyshomeostasis in such pathways remain to be addressed. Because cobalamin utilization is dependent on its efficient transit through lysosomes, and mounting evidence indicates that lysosomal function deteriorates in aging long-lived post-mitotic cells such as neurons, in the present article we review published data that supports the proposition that impaired lysosomal processing of cobalamin may play a significant role in age-related (neuro) degenerative diseases.

Keywords

AgingLysosomesLipofuscinVitamin-B12Neurodegeneration

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Illawarra Health and Medical Research InstituteUniversity of WollongongWollongongAustralia
  2. 2.School of Biological SciencesUniversity of WollongongWollongongAustralia
  3. 3.Department of PharmacologyLinköping UniversityLinköpingSweden