Fig. 1.
Genetic composition of human mitochondria. a Dual-genome origins of the mitochondrial electron transport chain (ETC). The ETC comprises ~ 90 individual protein subunits, encoded by both nuclear (nDNA) and mitochondrial genomes (mtDNA). Assembly of a functional ETC requires co-ordinated regulation and expression of these components by the two separate genomes. Beyond the 13 ETC proteins encoded in mtDNA, the remainder of the human mitochondrial proteome is encoded in and expressed from the nuclear genome. Import of nuclear-encoded proteins through membrane-embedded protein translocases into the mitochondrial matrix requires a membrane potential between the intermembrane space (IMS) and the matrix (white circles). Nuclear encoded components coloured brown, mitochondria-encoded components in blue, red, green, and yellow by complex. Complex III is shown as a dimer. b Annotated genetic features of human mtDNA. Eleven mRNAs (two overlapping) encode 13 polypeptides forming essential components of the ETC. These are expressed using an altered genetic code, enabled by a full complement of 22 mitochondria-specific tRNAs also encoded in mtDNA. Resulting proteins are co-translationally inserted into the inner mitochondrial membrane (IMM) by mitochondrial ribosomes, which contain structural RNA components of exclusive mitochondrial origin (12S rRNA, 16S rRNA, and mt-tRNAVal). An expanded view of the displacement loop (D-loop) and major non-coding region (NCR), incorporating 7S DNA, with indication of key loci for mtDNA transcription (heavy strand promoter, HSP; light strand promoter, LSP), replication (origin of heavy strand, OH) and other prominent elements relevant to these functions (conserved sequence block 1–3, CSB1–3; termination-associated sequence, TAS). c Primary polycistronic maps of transcription of mtDNA from LSP and HSP. Near-complete genome length transcripts are produced through transcription by the mitochondrial RNA polymerase (POLRMT) mitochondrial transcription elongation factor (TEFM) complex, which undergo endonucleolytic processing to liberate individual gene products, and further modifications of mRNA, rRNA, and tRNA molecules to enable efficient translation