bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2021‒09‒12
three papers selected by
Gavin McStay
Staffordshire University

  1. J Am Assoc Nurse Pract. 2021 Sep 01. 33(9): 673-675
      ABSTRACT: The mitochondrial genome, which contains all of the hereditary information within human mitochondria, consists of 16,569 base pairs of double-stranded DNA that encode 37 genes. Pathogenic mutations of mitochondrial DNA (mtDNA) cause dysfunction of the respiratory chain and the process of oxidative phosphorylation (OXPHOS), leading to impaired adenosine triphosphate synthesis. Nuclear DNA (nDNA) mutations can affect structural subunits or assembly factors of one of the five OXPHOS complexes. Mitochondrial diseases are a heterogeneous group of disorders, ranging from mtDNA single-point mutations and large-scale deletions to mitochondrial depletion syndromes, resulting from nDNA pathogenic mutations. Manifestations of mitochondrial disease are multisystemic, and organs with substantial energy requirements are most typically affected. Mitochondrial disorders are progressive in nature, and prognosis is dependent on the organs involved and the rate and severity of disease progression. A multidisciplinary team approach is needed to monitor and manage disease sequelae.
  2. Mitochondrion. 2021 Sep 02. pii: S1567-7249(21)00116-1. [Epub ahead of print]
      In memoriam of Bernhard Kadenbach: Although the main focus of his research was the structure, function, and regulation of mitochondrial cytochrome c oxidase (CytOx), he earlier studied the mitochondrial phosphate carrier and found an essential role of cardiolipin. Later, he discovered tissue-specific and developmental-specific protein isoforms of CytOx. Defective activity of CytOx is found with increasing age in human muscle and neuronal cells resulting in mitochondrial diseases. Kadenbach proposed a theory on the cause of oxidative stress, aging, and associated diseases stating that allosteric feedback inhibition of CytOx at high mitochondrial ATP/ADP ratios is essential for healthy living while stress-induced reversible dephosphorylation of CytOx results in the formation of excessive reactive oxygen species that trigger degenerative diseases. This article summarizes the main discoveries of Kadenbach related to mammalian CytOx and discusses their implications for human disease.
  3. Front Mol Biosci. 2021 ;8 711227
      Copper is essential for life processes like energy metabolism, reactive oxygen species detoxification, iron uptake, and signaling in eukaryotic organisms. Mitochondria gather copper for the assembly of cuproenzymes such as the respiratory complex IV, cytochrome c oxidase, and the antioxidant enzyme superoxide dismutase 1. In this regard, copper plays a role in mitochondrial function and signaling involving bioenergetics, dynamics, and mitophagy, which affect cell fate by means of metabolic reprogramming. In mammals, copper homeostasis is tightly regulated by the liver. However, cellular copper levels are tissue specific. Copper imbalances, either overload or deficiency, have been associated with many diseases, including anemia, neutropenia, and thrombocytopenia, as well as tumor development and cancer aggressivity. Consistently, new pharmacological developments have been addressed to reduce or exacerbate copper levels as potential cancer therapies. This review goes over the copper source, distribution, cellular uptake, and its role in mitochondrial function, metabolic reprograming, and cancer biology, linking copper metabolism with the field of regenerative medicine and cancer.
    Keywords:  ROS; cancer; copper; differentiation; hematopoietic stem cells (HSCs); metabolic reprograming; mitochondria; proliferation