# MT-CYB

## Overview
The MT-CYB gene is a mitochondrial gene that encodes the protein cytochrome b, a key component of the mitochondrial electron transport chain, specifically within Complex III, also known as the cytochrome bc1 complex. Cytochrome b is a transmembrane protein that plays a crucial role in cellular respiration by facilitating electron transfer from ubiquinol to cytochrome c, a process that is coupled with proton translocation across the inner mitochondrial membrane. This function is essential for maintaining the proton gradient necessary for ATP synthesis, the primary energy currency of the cell. The MT-CYB gene is unique in its mitochondrial location and lack of introns, distinguishing it from its nuclear counterparts. Mutations in MT-CYB can lead to a variety of mitochondrial disorders and have been implicated in certain cancers, highlighting its importance in cellular energy metabolism and human health (Iommarini2017Mild; Meunier2013Respiratory).

## Structure
The MT-CYB gene encodes the cytochrome b protein, a crucial component of the mitochondrial electron transport chain, specifically within the cytochrome bc1 complex. The primary structure of cytochrome b consists of amino acid sequences encoded by mitochondrial DNA, forming a protein with a molecular mass of approximately 42.5 kDa (Berry2000Structure). 

The secondary structure of cytochrome b is dominated by alpha helices, with the protein containing eight transmembrane helices, designated A-H (Esposti1993Mitochondrial; Berry2000Structure). These helices are organized into two groups, contributing to the protein's role in electron transport (Xia1997Crystal). 

In terms of tertiary structure, cytochrome b's helices form a core that houses two heme groups, bL and bH, which are essential for its redox function (Berry2000Structure; Iwata1998Complete). The heme groups are ligated by histidine residues, and their planes are parallel to each other and perpendicular to the membrane (Berry2000Structure).

The quaternary structure involves cytochrome b's interaction with other subunits in the bc1 complex, forming part of the electron transport chain that facilitates ATP synthesis (Iwata1998Complete). The protein's structure is integral to its function in the Q-cycle mechanism, which involves two quinone binding sites (Berry2000Structure).

## Function
The MT-CYB gene encodes cytochrome b, a critical component of the mitochondrial respiratory chain's Complex III (CIII), also known as the cytochrome bc1 complex. This protein plays a vital role in cellular respiration by facilitating the transfer of electrons from ubiquinol to cytochrome c, a process that is coupled with the translocation of protons across the inner mitochondrial membrane. This activity is essential for generating a proton gradient, which is crucial for ATP synthesis, the primary energy currency of the cell (Carossa2014A; Meunier2013Respiratory).

Cytochrome b, along with other subunits like the Rieske iron-sulfur protein and cytochrome c1, forms the catalytic core of CIII. It is involved in the Q-cycle, a mechanism that contributes to the generation of the mitochondrial proton motive force by oxidizing ubiquinol and reducing cytochrome c (Iommarini2017Mild). The proper assembly of CIII into supercomplexes with Complex I and Complex IV is important for efficient electron channeling and reducing reactive oxygen species overproduction (Iommarini2017Mild).

The MT-CYB gene is located on the mitochondrial DNA and is unique in that it does not contain introns, unlike its yeast counterpart (Meunier2013Respiratory). Variations in this gene can lead to mitochondrial diseases and have been associated with specific cancers, affecting the function of CIII and potentially impacting cell fitness and health under adverse conditions (Meunier2013Respiratory).

## Clinical Significance
Mutations in the MT-CYB gene, which encodes a component of mitochondrial complex III, are associated with a range of clinical disorders. These include multisystem disorders characterized by exercise intolerance, visual defects, and mild cardiomyopathy, as seen in a case involving a novel in-frame 18-bp microdeletion (Carossa2014A). MT-CYB mutations can also lead to mitochondrial encephalomyopathy, as demonstrated by a stop-codon mutation resulting in complex III deficiency and severe exercise intolerance (Keightley2000Mitochondrial). 

In the context of male infertility, single nucleotide variants (SNPs) in MT-CYB have been linked to impaired sperm motility and function, potentially due to altered gene expression and ATP production (Saleh2022Association). MT-CYB mutations are implicated in hypertrophic cardiomyopathy (HCM), where they disrupt protein structure and mitochondrial function (Hagen2013MT‐CYB). 

Alterations in MT-CYB expression have been observed in colorectal adenocarcinomas, where increased expression is associated with tumor progression (Wallace2016Expression). In non-alcoholic fatty liver disease (NAFLD), MT-CYB mutations correlate with disease severity and metabolic dysfunction (Pirola2020Liver). These findings underscore the gene's clinical significance in various mitochondrial and metabolic disorders.

## Interactions
The MT-CYB gene encodes cytochrome b, a critical component of mitochondrial complex III, also known as the cytochrome bc1 complex. This complex is essential for the mitochondrial respiratory chain, facilitating electron transfer and contributing to ATP production. Cytochrome b interacts with other proteins within complex III, including cytochrome c1 and the Rieske iron-sulfur protein, to enable efficient electron transfer across the mitochondrial membrane (Protasoni2020Respiratory).

Mutations in MT-CYB can disrupt these interactions, leading to deficiencies in complex III and affecting the assembly and function of other mitochondrial complexes, such as complexes I and IV. The absence of MT-CYB results in the accumulation of assembly intermediates and prevents the formation of fully assembled complex III and its associated supercomplexes (Protasoni2020Respiratory). This disruption can also stall the assembly of complex I, as MT-CYB is crucial for the proper maturation of this complex (Protasoni2020Respiratory).

The interactions of cytochrome b within complex III are not only structural but also functional, as they influence the sensitivity of the complex to substrates and inhibitors. Understanding these interactions is vital for developing targeted therapies for mitochondrial diseases associated with MT-CYB mutations (Lloyd2013Structural).


## References


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