Mitochondrial genome articles from across Nature Portfolio

APOGEE 2 is a machine-learning tool for assessing the fragility of the mitochondrial genome, evaluating genetic variant pathogenicity and ultimately enhancing our understanding of the clinical heterogeneity of mitochondrial genetic diseases.

We quantify mitochondrial DNA copy number and heteroplasmy levels and study their association with nuclear genetic loci in population-scale biobanks.

While the organelle genome is commonly considered to be a single circular DNA molecule, extensive variation exists. Here, the authors report multipartite minicircular genomes in red algae and indicate an origin driven by recombination due to loss of DNA replication, recombination, and repair genes.

A paper in Molecular Cell reports the characterization of a second functional light strand promoter (LSP2) in the mitochondrial genome, challenging the view that mitochondrial DNA replication and gene expression are coupled by their reliance on a single light strand promoter (LSP).

The integrity of the mitochondrial genome (mitochondrial DNA) is crucial for energy synthesis in all complex life. A study now reveals a vicious cycle of mtDNA replication within dysfunctional mitochondria that preferentially propagates genomes carrying deleterious mutations.

A study in eLife identifies 71 nuclear loci associated with mitochondrial DNA copy number (mtDNA-CN) and reveals a putative causal role for mtDNA-CN in dementia.

Individual cells in the same induced pluripotent stem cell (iPSC)-derived clones can exhibit large heterogeneity. In this Comment, Carelli et al. discuss emerging evidence implicating variants in mitochondrial DNA, and highlight the need for routine screening of iPSCs.

This molecular phenotyping study shows that common variants in mitochondrial DNA associated with diseases of ageing influence cellular protein homeostasis, and that this link is mediated by circulating levels of N-formylmethionine, the initiating amino acid in mitochondrial protein synthesis.

Variants in mitochondrial DNA (mtDNA), which are detectable in whole-genome sequencing (WGS) data, can cause a wide range of phenotypes of varying severity. The authors call for a wider debate on the communication of uncertainties around mtDNA variants and the risks versus benefits of screening.