Friday, July 22, 2016

Labile Low-Molecular-Mass Metal Complexes in Mitochondria: Trials and Tribulations of a Burgeoning Field

Paul A. Lindahl and Michael J. Moore, Biochemistry, Article ASAP, DOI: 10.1021/acs.biochem.6b00216, Publication Date (Web): July 19, 2016

Iron, copper, zinc, manganese, cobalt, and molybdenum play important roles in mitochondrial biochemistry, serving to help catalyze reactions in numerous metalloenzymes.
The iron transported through the high-affinity importers mitoferrin 1 and 2 (or Mrs3/4) is ultimately utilized in the biosynthesis of ISC and heme cofactors. Indeed, the majority of Fe that accumulates in mitochondria of frataxin-deficient cells passes through these carrier proteins.
FeIII nanoparticles accumulate in the mitochondria of yeast cells lacking the frataxin homologue (Yfh1), which also contain deficient amounts of ISCs and hemes. What is less commonly realized is that Zn-protoporphyrin IX accumulates in mitochondria from this same strain. Curiously, excess ZnSO4 in the medium prevents the accumulation of Fe in mitochondria of Δyfh1 cells, increases the growth rate of this strain, and mitigates ROS damage. Surprisingly, these responses are not caused by an increase in ISC or heme synthesis, which makes them difficult to explain.