bims-humivi Biomed News
on Human mito-nuclear genetic interplay
Issue of 2026–03–15
two papers selected by
Mariangela Santorsola, Università di Pavia
  1. From disease prevention to fertility treatment: rethinking the use of mitochondrial donation for oocyte-related infertility in the light of safety and efficacy.
  2. ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms.
  1. Hum Reprod. 2026 Mar 13. pii: deag027. [Epub ahead of print]
    From disease prevention to fertility treatment: rethinking the use of mitochondrial donation for oocyte-related infertility in the light of safety and efficacy.
    Flor Pasturino, Guido M W R De Wert, Cathy Herbrand, Hubert J M Smeets.
      Maternal spindle transfer (MST) and pronuclear transfer (PNT) raise a number of important ethical and regulatory issues. These IVF procedures that transfer nuclear DNA to enucleated oocytes or zygotes aim to prevent transmitting mitochondrial disease by female carriers of mitochondrial DNA (mtDNA) mutations and enable them to have healthy genetically related children. MST/PNT might also prove effective in treating oocyte-related infertility, but are not permitted in the UK and Australia, unlike MST/PNT for mtDNA disorders. The paper discusses the regulation of MST/PNT for both applications in relation to their risks and efficacy, highlighting the scarcity of clinical data. Based on risk reduction, it has even been proposed to treat oocyte-related infertility first before moving to mtDNA disorders. We argue that a prohibition of MST/PNT for infertility is not justified, neither should it initially be applied only for infertility because of the little evidence yet available regarding its efficacy and potential risks. We propose a staged approach to identify MST/PNT-treatable causes of oocyte-related infertility first, followed by a preclinical study and clinical trial and, if positive, wider application. Importantly, we call for transparency in publishing regular trial results, deeper ethical reflection, and more consistent policies that consider comparable uncertainties in mtDNA disorders and oocyte-related infertility.
    Keywords:  assisted reproduction; ethics; maternal spindle transfer; mitochondria; mitochondrial DNA disorders; mitochondrial donation; nuclear transfer; oocyte-related infertility; pronuclear transfer; translational research
    DOI:  https://doi.org/10.1093/humrep/deag027
  2. Cell Rep. 2026 Mar 06. pii: S2211-1247(26)00104-X. [Epub ahead of print]45(3): 117026
    ADAR1 regulates dsRNA formation in nuclear and mitochondrial transcripts through editing-dependent and -independent mechanisms.
    Heegwon Shin, Tyler J Dorrity, Justin Aruda, Kenenni A Wiegand, Jung Seung Nam, Jiping Yang, Aidan S Jones, Jake A Gertie, Meera K Singh, Yuanjun Yin, Keer He, Rafan Sarker, Rajesh K Soni, Yousin Suh, Iok In Christine Chio, Silvi Rouskin, Hachung Chung.
      Endogenous (self) double-stranded RNAs (dsRNAs) in human cells can activate innate immune responses. ADAR1, an A-to-I editing enzyme of dsRNAs, suppresses aberrant immune activation by self-dsRNAs. However, how ADAR1 influences the cellular dsRNA landscape remains unclear. We show that human ADAR1 downregulates self-dsRNA abundance through editing-dependent and editing-independent mechanisms. We further conducted quantitative dsRNA sequencing on wild-type and ADAR1-deficient cells. dsRNAs are enriched in protein-coding mRNAs-especially those with repetitive elements and elongated 3' UTRs-and mitochondrial RNAs. ADAR1-regulated dsRNA transcripts consist of nuclear-encoded mRNAs and, unexpectedly, mitochondria-encoded RNAs rarely edited by ADAR1. Accordingly, dsRNAs accumulate to high levels within the mitochondria of ADAR1-deficient cells. Mass spectrometry and biochemical assays can detect ADAR1p150 in mitochondrial fractions. Notably, ADAR1 loss sensitizes cells to inflammation under mitochondrial stress (e.g., herniation and X-ray irradiation). Hence, we show that dsRNAs regulated by ADAR1 go beyond A-to-I edited transcripts and that ADAR1 can control mitochondrial dsRNAs.
    Keywords:  A-to-I editing; ADAR1; AGS; Aicardi-Goutieres syndrome; CP: immunology; CP: molecular biology; IFN; PKR; double-stranded RNA; dsRNA; dsRNA-seq; innate immunity; mitochondria; mitochondrial stress; protein kinase R; type 1 interferon
    DOI:  https://doi.org/10.1016/j.celrep.2026.117026
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