Human mitochondrial COX1 assembly into cytochrome c oxidase at a glance

Abstract

Mitochondria provide the main portion of cellular energy in form of ATP produced by the F 1 F o ATP synthase, which uses the electrochemical gradient, generated by the mitochondrial respiratory chain (MRC). In human mitochondria, the MRC is composed of four multisubunit enzyme complexes, with the cytochrome c oxidase (COX, also known as complex IV) as the terminal enzyme. COX comprises 14 structural subunits, of nuclear or mitochondrial origin. Hence, mitochondria are faced with the predicament of organizing and controlling COX assembly with subunits that are synthesized by different translation machineries and that reach the inner membrane by alternative transport routes. An increasing number of COX assembly factors have been identified in recent years. Interestingly, mutations in several of these factors have been associated with human disorders leading to COX deficiency. Recently, studies have provided mechanistic insights into crosstalk between assembly intermediates, import processes and the synthesis of COX subunits in mitochondria, thus linking conceptually separated functions. This Cell Science at a Glance article and the accompanying poster will focus on COX assembly and discuss recent discoveries in the field, the molecular 1 Department of Cellular Biochemistry, University Medical Center Gö ttingen, 37073 Gö ttingen, Germany.2 Max-Planck Institute for Biophysical Chemistry, 37077 Gö ttingen, Germany. Journal of Cell Science functions of known factors, as well as new players and control mechanisms. Furthermore, these findings will be discussed in the context of human COX-related disorders.

Exploring the mitochondrial microRNA import pathway through Polynucleotide Phosphorylase (PNPase)

“…Das et al found an increase in miRNA-181c in cardiomyocyte mitochondria during heart failure, which targets and represses mitochondrial cytochrome c oxidase 1 (mtCOX1), an important component of ETC complex IV [27,28,30]. Further, the role of miRNA-378 in controlling metabolic processes through targeting mediator complex subunit 13 (Med13) in the liver and insulin-like growth factor 1 (IGF-1) and ATP6 in the heart has been demonstrated [18,50,53].…”

Mitochondrial DNA Hypomethylation Is a Biomarker Associated with Induced Senescence in Human Fetal Heart Mesenchymal Stem Cells

“…COX1 encodes cytochrome c oxidase I, the main subunit of the cytochrome c oxidase complex, which is a key enzyme in aerobic metabolism [62]. The proton pumping heme-copper oxidase represents the terminal, energy-transfer enzyme of respiratory chains in both prokaryotes and eukaryotes.…”

The mitochondrion: a central architect of copper homeostasis

“…COX assembly as a whole is a complex, modular process that has been thoroughly reviewed by others. 25–27 Complex biogenesis relies on more than 30 accessory proteins that function collectively to coordinate the ordered incorporation of structural subunits with the synthesis, delivery and insertion of prosthetic groups. The two copper sites of the holoenzyme are matured in the IMS by a suite of evolutionarily conserved COX assembly factors, with Cu B site formation requiring at least COX17, COX19 and COX11 function and Cu A site maturation depending on at least COX17, SCO1, SCO2 and COA6 function (Figure 1).…”