The
biological importance of
manganese lies in its function as a key cofactor for numerous metalloenzymes and as non-enzymatic
antioxidant. Due to these two essential roles, it appears evident that disturbed
manganese homeostasis may trigger the development of pathologies in humans. In this context, yeast has been extensively used over the last decades to gain insight into how cells regulate intra-organellar
manganese concentrations and how human pathologies may be related to disturbed cellular
manganese homeostasis. This review first summarizes how
manganese homeostasis is controlled in yeast cells and how this knowledge can be extrapolated to human cells. Several
manganese-related pathologies whose molecular mechanisms have been studied in yeast are then presented in the light of the function of this
cation as a non-enzymatic
antioxidant or as a key cofactor of metalloenzymes. In this line, we first describe the Transmembrane
protein 165-Congenital Disorder of Glycosylation (TMEM165-CDG) and
Friedreich ataxia pathologies. Then, due to the established connection between
manganese cations and neurodegeneration, the
Kufor-Rakeb syndrome and
prion-related diseases are finally presented.