bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2025–11–23
two papers selected by
Mariangela Santorsola, Università di Pavia
  1. A record-setting mitogenome in the holoparasitic plant Balanophora yakushimensis accompanied by exceptional loss of organellar DNA repair and recombination genes.
  2. Decoding nuclear-encoded mitochondrial genes in major depressive disorder: A multi-omics perspective.
  1. BMC Biol. 2025 Nov 18. 23(1): 344
    A record-setting mitogenome in the holoparasitic plant Balanophora yakushimensis accompanied by exceptional loss of organellar DNA repair and recombination genes.
    Runxian Yu, Xueke Zhi, Luis Federico Ceriotti, Elizabeth Skippington, Danny W Rice, Huei-Jiun Su, Todd J Barkman, Chenyu Sun, Ying Liu, Dongming Fang, Xiaoli Chen, Claude W dePamphilis, Jeffrey P Mower, M Virginia Sanchez-Puerta, Jeffrey D Palmer, Renchao Zhou.
       BACKGROUND: Despite only limited sampling, the holoparasitic plant family Balanophoraceae harbors extreme mito-genome diversity and also has exceptionally divergent plastomes. We therefore sequenced the mitochondrial, plastid, and nuclear genomes of Balanophora yakushimensis and its transcriptome.
    RESULTS: At 1.1 Mb, the B. yakushimensis mitogenome is one of the largest known mitogenomes. Driving this expansion and generating the most repeat-rich mitogenome in land plants are many large (up to 200 kb) duplications and a massive proliferation of short, AT-rich repeated sequences. The repeat proliferation, in conjunction with a highly elevated and unusually AT-biased mutation rate, has produced what is by far the most AT-rich land-plant mito-genome. These invasive repeats also created giant introns, unprecedented in size for organelles, and greatly expanded all rDNA exons. We discovered a record-low, for all genomes, transition/transversion ratio (0.12) in B. yakushimensis mtDNA and documented a 26-fold range in this ratio across angiosperm mitogenomes. The B. yakushimensis nuclear genome has lost exceptionally many genes that function in organellar DNA recombination, repair, and replication (RRR). We discuss ways in which these losses-and other genetic alterations as well as non-genetic ones-may or may not be related to the unusual features of both its mitochondrial and plastid genomes.
    CONCLUSIONS: The mitogenome of B. yakushimensis possesses many exceptional, indeed record-setting properties. The unprecedented loss of nuclear genes for organellar DNA RRR may explain some of these unusual features. These findings expand the boundaries of mitogenome deviancy and raise outstanding questions about the forces driving such extravagantly diversifying evolution.
    Keywords:  AT-biased base composition; Mitochondrial genomes; Mutation spectrum; Parasitic plants; Photolyases; Repeated sequences
    DOI:  https://doi.org/10.1186/s12915-025-02449-8
  2. Psychol Med. 2025 Nov 18. 55 e350
    Decoding nuclear-encoded mitochondrial genes in major depressive disorder: A multi-omics perspective.
    Jing Liao, Xianyan Wang, Gaokun Dai, Huilei Xu, Fuchao Zhang, Xiang Yuan, Qiuxia Feng.
       BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of major depressive disorder (MDD); however, the causal contributions of specific mitochondrial genes across regulatory layers remain unclear.
    METHODS: We integrated genome-wide association study summary statistics from the Psychiatric Genomics Consortium and FinnGen with quantitative-trait-locus (QTL) datasets for DNA methylation, gene expression (eQTL), and protein abundance. Mitochondrial genes were annotated using the MitoCarta3.0 database. Summary-based Mendelian randomization and Bayesian colocalization were applied to assess causal relationships, with colocalization determined by the posterior probability of a shared causal variant (PPH4), and the false discovery rate used for multiple-testing correction. Brain-specific effects were evaluated using Genotype-Tissue Expression eQTL data. Prioritized genes were ranked based on cross-omics consistency and replication evidence.
    RESULTS: Five mitochondrial genes were prioritized. TDRKH showed consistent associations across methylation, transcription, and protein levels, with hypermethylation at cg24503712 linked to reduced expression and a lower risk of MDD (Tier 1). METAP1D (Tier 2) demonstrated protective effects at both the transcript and protein levels. LONP1, FIS1, and SCP2 (Tier 3) exhibited consistent but complex regulatory patterns. Several signals were replicated in brain tissues, including TDRKH in the caudate and METAP1D in the cortex.
    CONCLUSIONS: This study provides multi-omics evidence for the causal involvement of mitochondrial genes in MDD. TDRKH and METAP1D emerged as key candidates, offering promising targets for future mechanistic research and therapeutic development.
    Keywords:  GWAS; major depressive disorder; mitochondrial genes; summary-based Mendelian randomization
    DOI:  https://doi.org/10.1017/S0033291725102559
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