bims-cytox1 Biomed news on
Cytochrome oxidase subunit 1
Issue of 2017‒07‒14
six papers selected by
Gavin McStay
New York Institute of Technology


  1. J Biol Chem. 2017 Jul 07. doi: 10.1074/jbc.R117.791061
    Abstract:  Mitochondria are multifaceted and indispensable organelles required for cell performance. Accordingly, dysfunction to mitochondria can result in cellular decline and possibly the onset of disease. Cells use a variety of means to recover mitochondria and restore homeostasis including the activation of retrograde pathways such as the mitochondrial unfolded protein response (UPRmt). In this minireview, we will discuss how cells adapt to mitochondrial stress through UPRmt regulation. Furthermore, we will explore the current repertoire of biological functions that are associated with this essential stress response pathway.
    Keywords:  Mitochondrial dysfunction; cell metabolism; cell signaling; cellular regulation; mitochondria; mitochondrial quality control; mitochondrial stress signaling; mitochondrial unfolded protein response; stress response
  2. Mitochondrion. 2017 Jul 04. doi: 10.1016/j.mito.2017.06.007
    Abstract:  Recessive mutations in EXOSC3, encoding a subunit of the human RNA exosome complex, cause pontocerebellar hypoplasia type 1b (PCH1B). We report a boy with severe muscular hypotonia, psychomotor retardation, progressive microcephaly, and cerebellar atrophy. Biochemical abnormalities comprised mitochondrial complex I and pyruvate dehydrogenase complex (PDHc) deficiency. Whole exome sequencing uncovered a known EXOSC3 mutation p.(D132A) as the underlying cause. In patient fibroblasts, a large portion of the EXOSC3 protein was trapped in the cytosol. MtDNA copy numbers in muscle were reduced to 35%, but mutations in the mtDNA and in nuclear mitochondrial genes were ruled out. RNA-Seq of patient muscle showed highly increased mRNA copy numbers, especially for genes encoding structural subunits of OXPHOS complexes I, III, and IV, possibly due to reduced degradation by a dysfunctional exosome complex. This is the first case of mitochondrial dysfunction associated with an EXOSC3 mutation, which expands the phenotypic spectrum of PCH1B. We discuss the links between exosome and mitochondrial dysfunction.
    Keywords:  Complex I deficiency; Human RNA exosome complex; Mitochondrial disease; Pontocerebellar hypoplasia type 1; Pyruvate dehydrogenase deficiency; Transcriptome analysis; Whole exome sequencing; mtDNA copy numbers
  3. Sci Rep. 2017 Jul 07. doi: 10.1038/s41598-017-05150-17(1):
    Abstract:  Growing evidence supports a general hypothesis that aging and cancer are diseases related to energy metabolism. However, the involvement of Fanconi Anemia (FA) signaling, a unique genetic model system for studying human aging or cancer, in energy metabolism remains elusive. Here, we report that FA complementation group D2 protein (FANCD2) functionally impacts mitochondrial ATP production through its interaction with ATP5α, whereas this relationship was not observed in the mutant FANCD2 (K561R)-carrying cells. Moreover, while ATP5α is present within the mitochondria in wild-type cells, it is instead located mostly outside in cells that carry the non-monoubiquitinated FANCD2. In addition, mitochondrial ATP production is significantly reduced in these cells, compared to those cells carrying wtFANCD2. We identified one region (AA42-72) of ATP5α, contributing to the interaction between ATP5α and FANCD2, which was confirmed by protein docking analysis. Further, we demonstrated that mtATP5α (∆AA42-72) showed an aberrant localization, and resulted in a decreased ATP production, similar to what was observed in non-monoubiquitinated FANCD2-carrying cells. Collectively, our study demonstrates a novel role of FANCD2 in governing cellular ATP production, and advances our understanding of how defective FA signaling contributes to aging and cancer at the energy metabolism level.
  4. Semin Cancer Biol. 2017 Jul 04. doi: 10.1016/j.semcancer.2017.06.014
    Abstract:  Oncocytomas are distinct tumors characterized by an abnormal accumulation of defective and (most probably) dysfunctional mitochondria in cell cytoplasm of such tumors. This particular phenotype has been studied for the last decades and the clarification of the etiopathogenic causes are still needed. Several mechanisms involved in the formation and maintenance of oncocytomas are accepted as reasonable causes, but the relevance and contribution of each one for oncocytic transformation may depend on different cancer etiopathogenic contexts. In this review, we describe the current knowledge of the etiopathogenic events that may lead to oncocytic transformation and discuss their contribution for tumor progression and mitochondrial accumulation.
    Keywords:  Autophagy; Mitochondria-rich tumors; Mitophagy; Oncocytomas; mtDNA
  5. Clin Sci (Lond). 2017 Aug 01. doi: 10.1042/CS20160940131(15):
    Abstract:  Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies. However, the impact of sexual dimorphism in this context is less clear, with several studies reporting conflicting observations. For instance in ageing studies, a rodent model reported female muscles have higher antioxidant capacity compared with males; in contrast, human studies demonstrate no sex difference in mitochondrial bioenergetics and oxidative damage. These divergent observations highlight the importance of considering models and methods used to examine mitochondrial function, when interpreting these data. The use of either isolated or intact mitochondrial preparations in many studies appears likely to be a source of discord, when comparing many studies. Overall, it is now clear that more research is needed to determine if sexual dimorphism is a contributing factor in the development of myopathologies.
    Keywords:  Skeletal muscle; mitochondria; sex