bims-curels Biomed News
on Leigh syndrome
Issue of 2024‒01‒14
four papers selected by
Cure Mito Foundation

  1. J Inflamm (Lond). 2024 Jan 11. 21(1): 1
      BACKGROUND: Mitochondrial diseases (MDs) are genetic disorders characterized by dysfunctions in mitochondria. Clinical data suggest that additional factors, beyond genetics, contribute to the onset and progression of this group of diseases, but these influencing factors remain largely unknown. Mounting evidence indicates that immune dysregulation or distress could play a role. Clinical observations have described the co-incidence of infection and the onset of the disease as well as the worsening of symptoms following infection. These findings highlight the complex interactions between MDs and immunity and underscore the need to better understand their underlying relationships.RESULTS: We used Ndufs4 KO mice, a well-established mouse model of Leigh syndrome (one of the most relevant MDs), to test whether chronic induction of a neuroinflammatory state in the central nervous system before the development of neurological symptoms would affect both the onset and progression of the disease in Ndufs4 KO mice. To this aim, we took advantage of the GFAP-IL6 mouse, which overexpresses interleukin-6 (IL-6) in astrocytes and produces chronic glial reactivity, by generating a mouse line with IL-6 overexpression and NDUFS4 deficiency. IL-6 overexpression aggravated the mortality of female Ndufs4 KO mice but did not alter the main motor and respiratory phenotypes measured in any sex. Interestingly, an abnormal region-dependent microglial response to IL-6 overexpression was observed in Ndufs4 KO mice compared to controls.
    CONCLUSION: Overall, our data indicate that chronic neuroinflammation may worsen the disease in Ndufs4 KO female mice, but not in males, and uncovers an abnormal microglial response due to OXPHOS dysfunction, which may have implications for our understanding of the effect of OXPHOS dysfunction in microglia.
    Keywords:  Astrocytes; GFAP-IL6; IL-6; Leigh syndrome; Microglia; Ndufs4 KO; Neuroinflammation
  2. Klin Onkol. 2023 ;37(4): 307-313
      BACKGROUND: Medical psychology research shows that how a patient communicates appears to be the strongest predictor of physician behavior during a consultation and that patient's activity also influences how much information a physician communicates to a patient about his or her illness and treatment. Thus, being a patient is a skill that needs to be developed to balance the responsibilities of doctors and patients in each of their encounters. There is a lack of clear recommendations and education in this area, and patients' behaviour is instead governed by the etiquette of courtesy.PURPOSE: The main aim of this article is to create a list of recommendations for patients and physicians to develop the skill of a competent patient in mutual communication and to include these recommendations into an educational leaflet with the aim to support the diagnostic and therapeutic process and personalized care.
    MATERIAL AND METHODS: Literature sources were selected unsystematically for the purpose of a narrative review, guided by the question: "What patient skills and competencies promote effective communication with the physician?" We adopted the snowball method, sometimes referred to as chain or reference selection, to generate the list.
    RESULTS: The results of the current narrative review demonstrate that the topic of patient communication competencies interests researchers and clinicians across medical disciplines. A summary of patient competencies was developed into an educational handout entitled "Before I go to the doctor". The leaflet can be freely distributed in a printed form, as presented in the article, or patients can be referred to its electronic version (via QR code on the leaflet or on the website of the Department of Medical Psychology and Psychosomatics of the Faculty of Medicine, Masaryk University, in the educational materials section at https: // The educational leaflet can be used as educational material in any healthcare facility.
    CONCLUSION: Being a competent patient is an ideal state that we strive for from the position of patients and physicians in order to develop medicine more symmetrically, in partnership and with an optimal distribution of responsibility for health, illness and treatment. The information leaflet is one of the possible and fundamental interventions to develop the skill of competent communication on the part of the patient. It is the most commonly used communication channel in patient education. The current list of recommendations is not definitive and binding. However, it opens up the topic itself. It names the dimensions of doctor-patient communication and gives both parties the opportunity to consider what their relationship should be like, what is missing in this relationship, and what is important to both parties.
    Keywords:  communication skills; competent patient; patient-centered care; responsibility in communication
  3. J Neurol Sci. 2024 Jan 06. pii: S0022-510X(24)00004-2. [Epub ahead of print]457 122869
      Mitochondrial DNA (mtDNA) is a 16,569 base pairs, double-stranded, circular molecule that contains 37 genes coding for 13 subunits of the respiratory chain plus 2 rRNAs and 22 tRNAs. Mutations in these genes have been identified in patients with a variety of disorders affecting every system in the body. The advent of next generation sequencing technologies has provided the possibility to perform the whole mitochondrial DNA sequencing, allowing the identification of disease-causing pathogenic variants in a single platform. In this study, the whole mtDNA of 100 patients from South Italy affected by mitochondrial diseases was analyzed by using an amplicon-based approach and then the enriched libraries were deeply sequenced on the ION Torrent platform (Thermofisher Scientific Waltham, MA, USA). After bioinformatics analysis and filtering, we were able to find 26 nonsynonymous variants with a MAF <1% that were associated with different pathological phenotypes, expanding the mutational spectrum of these diseases. Moreover, among the new mutations found, we have also analyzed the 3D structure of the MT-ATP6 A200T gene variation in order to confirm suspected functional alterations. This work brings light on new variants possibly associated with several mitochondriopathies in patients from South Italy and confirms that deep sequencing approach, compared to the standard methods, is a reliable and time-cost reducing strategy to detect all the variants present in the mitogenome, making the possibility to create a genomics landscape of mitochondrial DNA variations in human diseases.
    Keywords:  Deep sequencing; Mitochondrial DNA; Molecular signature; Protein 3D structure molecular analysis
  4. Clin Transl Med. 2024 Jan;14(1): e1523
      BACKGROUND: Epithelial ovarian cancer (EOC) heavily relies on oxidative phosphorylation (OXPHOS) and exhibits distinct mitochondrial metabolic reprogramming. Up to now, the evolutionary pattern of somatic mitochondrial DNA (mtDNA) mutations in EOC tissues and their potential roles in metabolic remodelling have not been systematically elucidated.METHODS: Based on a large somatic mtDNA mutation dataset from private and public EOC cohorts (239 and 118 patients, respectively), we most comprehensively characterised the EOC-specific evolutionary pattern of mtDNA mutations and investigated its biological implication.
    RESULTS: Mutational profiling revealed that the mitochondrial genome of EOC tissues was highly unstable compared with non-cancerous ovary tissues. Furthermore, our data indicated the delayed heteroplasmy accumulation of mtDNA control region (mtCTR) mutations and near-complete absence of mtCTR non-hypervariable segment (non-HVS) mutations in EOC tissues, which is consistent with stringent negative selection against mtCTR mutation. Additionally, we observed a bidirectional and region-specific evolutionary pattern of mtDNA coding region mutations, manifested as significant negative selection against mutations in complex V (ATP6/ATP8) and tRNA loop regions, and potential positive selection on mutations in complex III (MT-CYB). Meanwhile, EOC tissues showed higher mitochondrial biogenesis compared with non-cancerous ovary tissues. Further analysis revealed the significant association between mtDNA mutations and both mitochondrial biogenesis and overall survival of EOC patients.
    CONCLUSIONS: Our study presents a comprehensive delineation of EOC-specific evolutionary patterns of mtDNA mutations that aligned well with the specific mitochondrial metabolic remodelling, conferring novel insights into the functional roles of mtDNA mutations in EOC tumourigenesis and progression.
    Keywords:  epithelial ovarian cancer; evolutionary selection; metabolic remodelling; mitochondrial DNA; somatic mutations