| 2012 |
FAM36A/COX20 protein co-purifies with COX2, and patient fibroblasts lacking functional FAM36A accumulate COX1-containing CIV subassemblies that are almost devoid of COX2, establishing that COX20 is required for early incorporation of COX2 into the CIV assembly line. Lentiviral complementation with wild-type FAM36A restored CIV activity, holocomplex levels, and individual subunit amounts. |
Co-purification (co-IP), blue-native PAGE subassembly analysis in patient fibroblasts, lentiviral complementation |
Human molecular genetics |
High |
23125284
|
| 2014 |
COX20 acts as a chaperone that binds newly synthesized COX2 in the inner mitochondrial membrane and presents it to the copper metallochaperone module composed of SCO1 and SCO2, which act on COX20-bound COX2 to mature the CuA site before COX2 is incorporated into early CIV subassemblies. Loss of COX20 causes instability and degradation of COX2, producing CIV subassemblies containing COX1 and COX4 but lacking COX2, phenocopying SCO1/SCO2 patient cells. |
siRNA knockdown and TALEN knockout cell lines; immunoprecipitation of COX20-FLAG from stable knockout cells to identify COX20–COX2 interaction; BN-PAGE subassembly analysis |
Human molecular genetics |
High |
24403053
|
| 2011 |
In S. cerevisiae, Cox20 (the yeast ortholog) is required for three distinct steps in Cox2 biogenesis: (1) efficient cleavage of the Cox2 leader peptide by the Imp1 inner membrane protease; (2) export of the Cox2 C-tail by the Cox18 translocase — Cox20 co-immunoprecipitates with Cox18 in a Cox2-dependent manner, suggesting Cox20 binding accelerates Cox2 release from Cox18; and (3) protection of unassembled Cox2 from degradation by the i-AAA protease, as shown by partial bypass of cox20Δ growth defects by yme1, mgr1, or mgr3 mutations that reduce i-AAA protease activity. |
Co-immunoprecipitation (Cox20–Cox18 interaction); genetic epistasis (yme1/mgr1/mgr3 suppressor analysis); in vivo pulse-chase/leader peptide processing assay |
Genetics |
High |
22095077
|
| 2017 |
TMEM177 is a constituent of the COX20 interaction network in the inner mitochondrial membrane. Loss or overexpression of TMEM177 proportionally decreases or increases COX20 protein levels. TMEM177 associates with newly synthesized COX2 and with SCO2 in a COX20-dependent manner, and imbalance of TMEM177 causes accumulation of COX2 in a COX20-associated state, indicating TMEM177 promotes COX2 assembly specifically at the CuA-site formation step. |
Co-immunoprecipitation / interaction proteomics; siRNA knockdown and overexpression with quantitative Western blot; in-organello translation pulse-chase to track newly synthesized COX2 |
Biochimica et biophysica acta. Molecular cell research |
High |
29154948
|
| 2021 |
COX20 knockdown in ND7/23 sensory neuron cells causes complex IV deficiency with perturbed CIV assembly, reduced spare respiratory capacity, and reduced cell proliferation under metabolic stress, directly linking COX20 loss-of-function to mitochondrial bioenergetic dysfunction in sensory neurons. |
siRNA knockdown in neuronal cell line; BN-PAGE for CIV assembly; Seahorse XF respirometry; cell proliferation assay |
Brain : a journal of neurology |
Medium |
33751098
|
| 2019 |
In S. cerevisiae, COX20 overexpression rescues respiratory growth in Δimp1 and Δcox18 strains, confirming genetic interaction with these two essential CIV assembly factors (Imp1 inner membrane protease and Cox18 C-tail translocase). COX20 expression also reduces reactive oxygen species accumulation and apoptotic/necrotic cell death under hydrogen peroxide and metal-induced stress as measured by flow cytometry. |
Genetic epistasis (rescue of Δimp1 and Δcox18 respiratory defects by COX20 overexpression); flow cytometry ROS and viability assays |
Microorganisms |
Medium |
31752220
|
| 2022 |
Adenoviral overexpression of COX20 in patient fibroblasts carrying compound heterozygous COX20 variants partially restores COX20 protein levels, CIV assembly (BN-PAGE), CIV enzymatic activity, and mitochondrial oxygen consumption rate, confirming loss-of-function as the pathogenic mechanism. |
Adenoviral gene rescue; BN-PAGE; Seahorse XF mito stress test; enzymatic activity assay; Western blot |
Frontiers in neurology |
Medium |
35651336
|