# MICOS13

## Overview
MICOS13 is a gene that encodes the protein mitochondrial contact site and cristae organizing system subunit 13, also known as MIC13 or QIL1. This protein is a vital component of the MICOS complex, which is crucial for maintaining the structural integrity and function of mitochondria. MIC13 plays a significant role in the formation and stabilization of cristae junctions, which are essential for the proper organization of the mitochondrial inner membrane and are critical for mitochondrial respiratory function and ATP production (Urbach2021Conserved; Kishita2020A). As a transmembrane protein, MIC13 facilitates interactions between various subunits of the MICOS complex, contributing to its assembly and stability (Urbach2021Conserved). Mutations in the MICOS13 gene can lead to severe mitochondrial disorders, underscoring its importance in cellular energy production and overall mitochondrial health (Zeharia2016Mitochondrial; Kishita2020A).

## Function
MICOS13, also known as QIL1, is a crucial component of the mitochondrial contact site and cristae organizing system (MICOS) complex, which is essential for maintaining mitochondrial architecture and function. In healthy human cells, MICOS13 plays a significant role in the formation and stabilization of cristae junctions, structures within the mitochondria that are vital for proper mitochondrial inner membrane organization (Zeharia2016Mitochondrial; Kishita2020A). 

The MICOS complex, including MICOS13, is involved in maintaining the stability of certain subunits within the mitochondria, such as MIC10, MIC26, and MIC27, which are crucial for the structural integrity of the mitochondrial inner membrane (Zeharia2016Mitochondrial). MICOS13 acts as a bridge between two MICOS subcomplexes, facilitating interactions that are necessary for the assembly and stability of the complex (Urbach2021Conserved). 

The presence of MICOS13 is essential for maintaining cristae morphology, which is critical for mitochondrial respiratory function and ATP production (Urbach2021Conserved). Mutations or deficiencies in MICOS13 can lead to severe mitochondrial disorders, highlighting its importance in cellular energy production and overall mitochondrial health (Urbach2021Conserved; Kishita2020A).

## Clinical Significance
Mutations in the MICOS13 gene are associated with severe mitochondrial disorders, particularly mitochondrial DNA depletion syndrome (MTDPS) and hepato-encephalopathy. These conditions are characterized by a significant reduction in mitochondrial DNA copy number, leading to multiple organ failure and symptoms such as early-onset fatal liver disease, encephalopathy, hyperlactatemia, and 3-methylglutaconic aciduria (Kishita2020A). A specific frameshift variant, c.13_29del (p.Trp6Profs*71), results in a truncated MICOS13 protein, causing a loss of cristae structures in mitochondria and deficiencies in the mitochondrial respiratory chain (Kishita2020A). 

Another study identified a frameshift mutation, c.44delC, p.(Gly15Glufs*75), in the QIL1/MIC13 gene, leading to the destabilization of the MICOS complex and altered cristae morphology, which are critical for mitochondrial function (Zeharia2016Mitochondrial). This mutation is linked to severe psychomotor retardation and neurodegenerative disorders (Zeharia2016Mitochondrial). 

Additionally, a homozygous acceptor splice site alteration (c.260-2A>G) in MICOS13 has been associated with combined oxidative phosphorylation deficiency, resulting in severe metabolic acidosis and respiratory failure (Gedikbasi2023Clinical). These findings underscore the critical role of MICOS13 in maintaining mitochondrial integrity and its involvement in severe metabolic disorders when mutated.

## Interactions
MICOS13, also known as MIC13, is a critical component of the MICOS complex, which is essential for maintaining mitochondrial structure. It interacts with various subunits within the MICOS complex, including MIC10, MIC26, MIC25, and MIC60. These interactions are crucial for the stability and assembly of the MICOS complex. The N-terminal region and a middle stretch of MIC13 are particularly important for these interactions, as deletion variants lacking these regions show reduced or no interaction with these subunits (Urbach2021Conserved).

MIC13 contains two conserved motifs, GxxxG and WN, which are essential for its interaction with other MICOS subunits, particularly MIC10. These motifs facilitate the formation of MIC10-MIC13 dimers, and their absence results in the loss of this interaction. The GxxxG motif is known for its role in dimerization of transmembrane segments, affecting MIC13's association with the mitochondrial membrane and cristae morphology (Urbach2021Conserved).

MIC13 also interacts with outer membrane proteins such as SAMM50, MTX1, and MTX2, and matrix proteins like GK, DNAJC1, and TMEM11. These interactions are vital for the assembly and function of the MICOS complex and the maintenance of mitochondrial cristae structure (Urbach2021Conserved).


## References


[1. (Urbach2021Conserved) Jennifer Urbach, Arun Kumar Kondadi, Céline David, Ritam Naha, Kim Deinert, Andreas S. Reichert, and Ruchika Anand. Conserved gxxxg and wn motifs of mic13 are essential for bridging two micos subcomplexes. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1863(12):183683, December 2021. URL: http://dx.doi.org/10.1016/j.bbamem.2021.183683, doi:10.1016/j.bbamem.2021.183683. This article has 9 citations.](https://doi.org/10.1016/j.bbamem.2021.183683)

[2. (Zeharia2016Mitochondrial) Avraham Zeharia, Jonathan R Friedman, Ana Tobar, Ann Saada, Osnat Konen, Yacov Fellig, Avraham Shaag, Jodi Nunnari, and Orly Elpeleg. Mitochondrial hepato-encephalopathy due to deficiency of qil1/mic13 (c19orf70), a micos complex subunit. European Journal of Human Genetics, 24(12):1778–1782, August 2016. URL: http://dx.doi.org/10.1038/ejhg.2016.83, doi:10.1038/ejhg.2016.83. This article has 47 citations and is from a domain leading peer-reviewed journal.](https://doi.org/10.1038/ejhg.2016.83)

[3. (Gedikbasi2023Clinical) Asuman Gedikbasi, Guven Toksoy, Meryem Karaca, Cagri Gulec, Mehmet Cihan Balci, Dilek Gunes, Seda Gunes, Ayca Dilruba Aslanger, Gokcen Unverengil, Birsen Karaman, Seher Basaran, Mubeccel Demirkol, Gulden Fatma Gokcay, and Zehra Oya Uyguner. Clinical and bi-genomic dna findings of patients suspected to have mitochondrial diseases. Frontiers in Genetics, June 2023. URL: http://dx.doi.org/10.3389/fgene.2023.1191159, doi:10.3389/fgene.2023.1191159. This article has 2 citations and is from a peer-reviewed journal.](https://doi.org/10.3389/fgene.2023.1191159)

[4. (Kishita2020A) Yoshihito Kishita, Masaru Shimura, Masakazu Kohda, Masumi Akita, Atsuko Imai‐Okazaki, Yukiko Yatsuka, Yoko Nakajima, Tetsuya Ito, Akira Ohtake, Kei Murayama, and Yasushi Okazaki. A novel homozygous variant in micos13/qil1 causes hepato‐encephalopathy with mitochondrial dna depletion syndrome. Molecular Genetics & Genomic Medicine, August 2020. URL: http://dx.doi.org/10.1002/mgg3.1427, doi:10.1002/mgg3.1427. This article has 12 citations.](https://doi.org/10.1002/mgg3.1427)