| 2016 |
COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV, specifically promoting stabilization of the III2+IV supercomplex without affecting respirasome (I+III2+IV) formation or the biogenesis, stabilization, and function of individual OXPHOS complexes. |
Native gel electrophoresis, co-immunoprecipitation, and functional respiratory assays in human and mouse cells |
Cell reports |
High |
27545886
|
| 2014 |
The short COX7a2l isoform present in C57BL/6 mice does not prevent formation of complex IV-containing supercomplexes or respirasomes; supercomplex organization is independent of COX7a2l isoforms in mice. Loss of complex IV (via Lrpprc knockout) compromises respirasome formation. |
Multiple complementary experimental approaches including BN-PAGE, respirometry, and mouse knockout of Lrpprc in mice with different COX7a2l isoforms |
Cell metabolism |
High |
25470551
|
| 2018 |
COX7A2L-knockout (KO) HEK293T and U87 cells lack SC III2+IV but show enhanced complex III steady-state levels, activity, and assembly rate, normal de novo complex IV biogenesis, and delayed but ultimately normal respirasome steady-state levels; only larger megacomplexes (SCs I1-2+III2+IV2-n) were absent. Functional substrate-driven competition assays showed normal mitochondrial respiration under standard and stress conditions in COX7A2L-KO cells. |
CRISPR-Cas9 knockout, BN-PAGE, in-gel activity assays, radioactive pulse-chase assembly assays, Seahorse respirometry under multiple stress conditions |
Cell reports |
High |
30428348
|
| 2021 |
SILAC-based complexome profiling of SCAFI (COX7A2L) knockout HEK293T cells showed preferential loss of SC III2+IV and a minor subset of respirasomes, without affecting OXPHOS function. Approximately 70% of respirasomes in wild-type cells contain COX7A2 (not SCAFI) and are present at similar levels in SCAFI-KO cells, demonstrating co-existence of structurally distinct respirasomes defined by preferential binding of complex IV via COX7A2 rather than SCAFI. |
SILAC-based complexome profiling, CRISPR-Cas9 knockout, quantitative mass spectrometry |
Biochimica et biophysica acta. Bioenergetics |
High |
33727070
|
| 2016 |
In liver mitochondria of C57BL/6 mice (which lack functional SCAFI/COX7A2L protein due to a 6-bp deletion), complex IV is mainly present as monomers and dimers with only low amounts found in combination with complexes I and III, and the main supercomplex comprises only complexes I and III — supporting a role for COX7A2L/SCAFI in incorporating complex IV into supercomplexes. SCAFI heterozygosity reduced SCAFI protein but did not affect respirasome assembly. |
BN-PAGE, immunoblotting, comparison of mice with different SCAFI isoforms on Bcs1l mutant background |
PloS one |
Medium |
27997587
|
| 2016 |
COX7AR (COX7A2L) is incorporated into the mitochondrial COX complex under cellular stress that stimulates energy metabolism. Gain- and loss-of-function analysis demonstrated that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion, and promotes cellular energy production in human mammary epithelial cells. |
Gain- and loss-of-function (overexpression/siRNA knockdown), cellular energy production assays (OCR/ECAR), proliferation/invasion assays |
Scientific reports |
Medium |
27550821
|
| 2022 |
A 10-bp insertion in the COX7A2L 3' UTR increases mRNA stability and expression; human myotubes harboring this insertion have more supercomplexes and increased respiration. Specific reconstitution of Cox7a2l expression in C57BL/6J mice leads to higher maximal oxygen consumption, increased lean mass, and increased energy expenditure. Cox7a2l expression is induced specifically in mouse muscle upon exercise. |
cis-eQTL mapping, mRNA stability assays, Seahorse respirometry in human myotubes, Cox7a2l reconstitution in mice with metabolic phenotyping, BN-PAGE for supercomplex quantification |
Nature metabolism |
High |
36253618
|
| 2025 |
COX7RP (COX7A2L)-transgenic mice show elevated ATP and NAD+ levels, reduced ROS production, decreased senescence-associated β-galactosidase levels, and significant lifespan extension. snRNA-seq revealed downregulation of senescence-associated secretory phenotype (SASP) genes in old COX7RP-Tg white adipose tissue adipocytes. |
Transgenic mouse model, metabolic biochemistry (ATP, NAD+, ROS), β-galactosidase senescence assay, single-nucleus RNA sequencing |
Aging cell |
Medium |
41253741
|
| 2024 |
COX7A2L protein significantly accumulates in III2+IV1 respiratory supercomplexes specifically following sprint-interval training (SIT) but not moderate-intensity continuous training (MICT) in human skeletal muscle, indicating exercise-mode-specific regulation of COX7A2L incorporation into supercomplexes. |
Quantitative proteomics/complexome profiling of human skeletal muscle biopsies after 8-week training interventions |
bioRxivpreprint |
Medium |
bio_10.1101_2024.12.19.629456
|
| 2024 |
TCF4 transcriptionally regulates COX7A2L expression; TCF4 overexpression increases COX7A2L levels, and COX7A2L knockdown counteracts TCF4-induced promotion of Wnt/β-catenin signaling pathway proteins (c-myc, β-catenin, cyclin D1) and apoptosis in hypoxia/reoxygenation-treated cells. |
Overexpression and knockdown experiments, rescue assays, Western blotting for Wnt/β-catenin pathway proteins, apoptosis and proliferation assays |
PloS one |
Low |
39499704
|
| 2025 |
Overexpression and knockdown of COX7A2L in human AC16 cardiomyocytes did not significantly affect cell viability or mitochondrial function (oxygen consumption rate parameters), even under isoproterenol-stimulated increased energy demand — a negative result. |
Overexpression and knockdown validated by sandwich ELISA, MTT assay, Seahorse XF Cell Mito Stress Test with isoproterenol stimulation |
PloS one |
Medium |
40560843
|