About this Research Topic
The ability to rapidly exchange electrons makes transition metals versatile cofactors that participate in a plethora of redox reactions in mitochondria. For example, they constitute the core of the mitochondrial respiratory chain, which mediates electron flow through the redox centers composed of iron-sulfur clusters, copper ions and heme moieties. Beyond energy production, metalloproteome is also involved in mitochondrial protein synthesis as cofactors of mitochondrial ribosomes, in protein maturation and turnover as cofactors of metalloproteases, in defense against reactive oxidative stress as cofactors of mitochondrial superoxide dismutases, and other processes.
On the flip side, transition metals pose the threat of uncontrolled reduction of oxygen and generation of detrimental reactive oxygen species. Thus, handling of mitochondrial transition metals requires specialized molecular machineries that import and store metal ions, synthesize metal cofactors and safeguard their incorporation into designated metalloproteins. Not surprisingly, perturbation in mitochondrial metal homeostasis results in multiple diseases that often disable organs and tissues of high energetic demand such as brain and muscles. As such, understanding their etiology at the molecular level can yield novel therapeutic strategies in patients afflicted with mitochondrial disorders.
This Research Topic aims to present and summarize current knowledge on mechanisms that shape the mitochondrial metalloproteome with a special focus on new developments and emerging concepts in the field. Despite substantial progress, our understanding of the biogenesis and maintenance of the mitochondrial metalloproteome is far from complete. As we currently lack both the necessary resolution to discern it at the molecular level and the bigger picture to understand the role of mitochondria in cellular metal ion homeostasis, we would like to encourage and welcome all contemporary perspectives on biology of transition metals in mitochondria.
We welcome both Original Research and Review articles that cover the following topics:
• Mechanisms of metal transport across membranes and their distribution in mitochondria;
• Molecular machineries behind the synthesis of iron-sulfur clusters and heme;
• Specificity of metal cofactor trafficking and delivery to their target apoproteins;
• Functions of metal-containing proteins in the mitochondria;
• Mitochondrial and cellular mechanisms of metal ion homeostasis;
• Molecular mechanisms of diseases connected to mitochondrial metalloproteome;
• Evolution of molecular machineries required for transition metals handling.
Dr. Vishal M. Gohil is listed as an inventor on the patent application PCT/US2019/041571 submitted by Texas A&M University entitled ‘Compositions for the Treatment of Copper Deficiency and Methods of Use'.
Keywords: mitochondria, metalloproteome, iron-sulfur clusters, copper ions, heme moieties
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