Abstract
Mitochondria are the repository for various metabolites involved in diverse energy-generating processes, like the TCA cycle, oxidative phosphorylation, and metabolism of amino acids, fatty acids, and nucleotides, which rely significantly on flavoenzymes, such as oxidases, reductases, and dehydrogenases. Flavoenzymes are functionally dependent on biologically active flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN), which are derived from the dietary component riboflavin, a water soluble vitamin. Riboflavin regulates the structure and function of flavoenzymes through its cofactors FMN and FAD and, thus, protects the cells from oxidative stress and apoptosis. Hence, it is not surprising that any disturbance in riboflavin metabolism and absorption of this vitamin may have consequences on cellular FAD and FMN levels, resulting in mitochondrial dysfunction by reduced energy levels, leading to riboflavin associated disorders, like cataracts, neurodegenerative and cardiovascular diseases, etc. Furthermore, mutations in either nuclear or mitochondrial DNA encoding for flavoenzymes and flavin transporters significantly contribute to the development of various neurological disorders. Moreover, recent studies have evidenced that riboflavin supplementation remarkably improved the clinical symptoms, as well as the biochemical abnormalities, in patients with neuronopathies, like Brown-Vialetto-Van-Laere syndrome (BVVLS) and Fazio-Londe disease. This review presents an updated outlook on the cellular and molecular mechanisms of neurodegenerative disorders in which riboflavin deficiency leads to dysfunction in mitochondrial energy metabolism, and also highlights the significance of riboflavin supplementation in aforementioned disease conditions. Thus, the outcome of this critical assessment may exemplify a new avenue to enhance the understanding of possible mechanisms in the progression of neurodegenerative diseases and may provide new rational approaches of disease surveillance and treatment.
Highlights
Energy metabolism generally takes place across the plasma membrane in prokaryotes, whereas eukaryotes have a well-defined specialized organelle called the mitochondrion
Alper’s syndrome patients with mutations in POLG may undergo complex I deficiency [53]. Since it involves complex I and IV dysfunction, riboflavin could play a possible role in its regulation, which corroborates with the study carried out in C. elegans where riboflavin supplementation enhanced the assembly of complex I and IV that further resulted in reduced oxidative stress and increased metabolic functions [39]
There is a gathering body of evidence which links the interaction between riboflavin and flavoproteins to the protection of neuronal cells from death by oxidative stress and apoptosis
Summary
Energy metabolism generally takes place across the plasma membrane in prokaryotes, whereas eukaryotes have a well-defined specialized organelle called the mitochondrion. Mitochondria are the energy-transducing mobile organelles in eukaryotic cells that produce ATP through the process of oxidative phosphorylation, which drives cellular metabolism [1]. It acts as a site of various metabolic processes, like the breakdown of sugars and long-chain fatty acids, the synthesis. The mitochondrial genome is a small circular DNA with a size of 16.5 kb [2] that contains 13 polypeptides encoding seven subunits of complex I, one subunit of complex III, three subunits of complex IV, and two subunits of complex V in respiratory chain while genes involved in complex II are encoded by the nuclear DNA. We discuss the new insights of mitochondrial biology in neurodegenerative diseases
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