bims-resufa Biomed News
on Respiratory supercomplex factors
Issue of 2025–11–30
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. The internal alternative NADH dehydrogenase (Ndi1) is the electron input in the Saccharomyces cerevisiae respirasome.
  2. The Role of Mitochondrial Complexes in Liver Diseases.
  1. Biochim Biophys Acta Bioenerg. 2025 Nov 21. pii: S0005-2728(25)00040-4. [Epub ahead of print] 149574
    The internal alternative NADH dehydrogenase (Ndi1) is the electron input in the Saccharomyces cerevisiae respirasome.
    Italo Lorandi, José Alfredo Hernández-Zúñiga, Mercedes Esparza-Perusquía, Genaro Matus-Ortega, Héctor Vázquez-Meza, Héctor Flores-Herrera, Juan Pablo Pardo, Federico Martínez, Oscar Flores-Herrera.
      Complex I is absent in mitochondria from Saccharomyces cerevisiae; instead, three rotenone-insensitive NADH dehydrogenases are present: two on the external (Nde1 and Nde2) and one on the internal (Ndi1) leaf of the inner mitochondrial membrane. In a previous work (1), we reported the presence of a supercomplex in S. cerevisiae constituted by the Ndi1 and complexes III2 and IV with an apparent MW of 1600 kDa. In this work, respirasomes from WT and NDE1Δ/NDE2Δ strains were isolated, and their activities characterized. Kinetic characterization of NADH:DBQ oxidoreductase activity from respirasomes, as well as free Ndi1, showed Vmax values of 0.85 ± 0.01, 0.82 ± 0.02, and 0.51 ± 0.02 μmol NADH oxidized·min-1·mg-1 for WT respirasome, NDE1Δ/NDE2Δ respirasome, and free Ndi1, respectively. The kinetic model for WT- and NDE1Δ/NDE2Δ respirasome was a Ping Pong BiBi mechanism with two different stable enzyme forms, free (E) and modified enzyme (F); while the free Ndi1 exhibited a Random BiBi mechanism with the ternary complex NADH-Ndi1-ubiquinone. This suggests that the interaction of Ndi1 with complexes III2 and IV in the respirasome modifies its kinetic mechanism. Oxygen consumption values were 0.35 ± 0.07 and 0.34 ± 0.07 μmol O2·min-1·mg-1 for WT and NDE1Δ/NDE2Δ respirasomes, respectively. The values for NADH/O2 ratio were 2.4 ± 1.4 and 2.4 ± 1.6 for WT and NDE1Δ/NDE2Δ respirasomes, respectively, suggesting that electron flux from NADH to oxygen occurs in the S. cerevisiae respirasome. The electron transfer from NADH to oxygen was inhibited by flavone, antimycin A, or cyanide, but the NADH dehydrogenase activity of the respirasome was insensitive to antimycin A or cyanide, indicating that no codependence of respirasomal-Ndi1 activity occurs as reported in the Ustilago maydis respirasome. This result indicates that the activity of respirasomal Ndi1 may contribute to the quinol pool with no evidence of direct substrate channeling. This is the first evidence of the Ndi1 role as the electron input in the respirasome from S. cerevisiae.
    Keywords:  Ndi1; Respirasome; Respiratory supercomplexes; Saccharomyces cerevisiae mitochondria
    DOI:  https://doi.org/10.1016/j.bbabio.2025.149574
  2. J Clin Transl Hepatol. 2025 Nov 28. 13(11): 976-985
    The Role of Mitochondrial Complexes in Liver Diseases.
    Hai An.
      Mitochondrial respiratory complexes (Complexes I-V) and their assembly into respiratory supercomplexes (SCs) are fundamental to liver bioenergetics, redox homeostasis, and metabolic adaptability. Disruption of these systems contributes to major liver diseases, including non-alcoholic fatty liver disease, alcoholic liver disease, drug-induced liver injury, viral hepatitis, and hepatocellular carcinoma, by impairing adenosine triphosphate synthesis, increasing oxidative stress, and altering metabolic pathways. Recent advances have clarified the structural-functional interdependence of individual complexes within SCs, revealing their dynamic remodeling in response to physiological stress and pathological injury. These insights open opportunities for clinical translation, such as targeting SC stability with pharmacological agents, nutritional strategies, or gene therapy, and employing mitochondrial transplantation in cases of severe mitochondrial failure. Precision medicine approaches, incorporating multi-omics profiling and patient-derived models, may enable individualized interventions and early detection using SC integrity as a biomarker. By linking molecular mechanisms to therapeutic strategies, this review underscores the potential of mitochondrial-targeted interventions to improve outcomes in patients with liver disease.
    Keywords:  ATP; ATP production; Adenosine triphosphate; Electron transfer chain; Energy metabolism; Liver disease; Mitochondrial complex
    DOI:  https://doi.org/10.14218/JCTH.2025.00194
This page is being maintained by Thomas Krichel. It was last updated on 2025‒12‒14 at 22:23.