Mitochondrial ribosomes in cancer

Kim, Hyun Jung; Maiti, Priyanka; Barrientos, Antoni

doi:10.1016/j.semcancer.2017.04.004

Cited by 137 publications

(124 citation statements)

References 166 publications

(234 reference statements)

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“…Mitochondria, also referred to as the 'cellular power centers', are semiautonomous, self-reproducing organelles found in the cytoplasm of most eukaryotes 108 , 109 . Mitochondria can generate high quantities of ATP for various biological actions in both physiological and pathological conditions 110 .…”

Section: Regulation Of Ampk In Ischemic Strokementioning

confidence: 99%

AMPK: Potential Therapeutic Target for Ischemic Stroke

et al. 2018

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5'-AMP-activated protein kinase (AMPK), a member of the serine/threonine (Ser/Thr) kinase group, is universally distributed in various cells and organs. It is a significant endogenous defensive molecule that responds to harmful stimuli, such as cerebral ischemia, cerebral hemorrhage, and, neurodegenerative diseases (NDD). Cerebral ischemia, which results from insufficient blood flow or the blockage of blood vessels, is a major cause of ischemic stroke. Ischemic stroke has received increased attention due to its '3H' effects, namely high mortality, high morbidity, and high disability. Numerous studies have revealed that activation of AMPK plays a protective role in the brain, whereas its action in ischemic stroke remains elusive and poorly understood. Based on existing evidence, we introduce the basic structure, upstream regulators, and biological roles of AMPK. Second, we analyze the relationship between AMPK and the neurovascular unit (NVU). Third, the actions of AMPK in different phases of ischemia and current therapeutic methods are discussed. Finally, we evaluate existing controversy and provide a detailed analysis, followed by ethical issues, potential directions, and further prospects of AMPK. The information complied here may aid in clinical and basic research of AMPK, which may be a potent drug candidate for ischemic stroke treatment in the future.

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Section: Regulation Of Ampk In Ischemic Strokementioning

confidence: 99%

AMPK: Potential Therapeutic Target for Ischemic Stroke

et al. 2018

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“…It is, however, unlikely that these potential pro-apoptotic functions can contribute to the proliferation defects seen after DHX30 depletion, given that their expression is not significantly modified. The expression of several mito-ribosome components has been evaluated as potential biomarkers associated with cancer clinical variables 32 .…”

Section: Discussionmentioning

confidence: 99%

DHX30 coordinates cytoplasmic translation and mitochondrial function contributing to cancer cell survival

Bosco

Rossi

Rizzotto

et al. 2020

Preprint

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DHX30 was recently identified as a critical element of an RBP complex participating in translational control of mRNAs containing a target 3’UTR cis element, in the context of p53-dependent apoptosis. Here we show that DHX30 exhibits a more general, housekeeping function that comprises a combination of activities exerted by an isoform expressed in the cytoplasm and one, more abundant, localized in the mitochondria. Stable HCT116 cells depleted of both DHX30 isoforms showed constitutive changes in the repertoire of mRNAs associated with polysomes and enhanced translation of mRNAs coding for cytoplasmic ribosomal proteins. On the contrary, nuclear-encoded mitoribosome transcripts showed reduced translation efficiency in DHX30-depleted cells. Furthermore, HCT116 shDHX30 cells exhibited increased rRNA synthesis, higher amounts of ribosomes, and increased global translation. Surprisingly, they also showed reduced proliferation, which was also observed upon transient silencing of just the DHX30 cytoplasmic transcript. HCT116 DHX30-depleted cells showed reduced mitochondrial energy metabolism, based on oxygen consumption rate, but did not show evidence of compensatory glycolysis. Impaired mitochondrial function was also related to decreased expression of mitochondrially encoded OXPHOS components. Results were extended to U2OS and MCF7 cell lines. A gene signature comprising DHX30 and fourteen mitoribosome transcripts that are candidate direct DHX30 targets showed prognostic value in distinct cancer types from TGCA data, with higher expression being associated to reduced overall survival. Hence, it appears that DHX30 contributes to cell homeostasis through the coordination between ribosome biogenesis, global translation, and mitochondrial functions. Targeting DHX30 could, thus, expose a vulnerability in cancer cells.

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“…Additionally, the literature suggests interaction between CCND1 , NADSYN1 and MRPL20 in signature C8 41,42 . NADSYN1 has been proposed as target of inhibitory therapy in cancer 43 , while MRPL20 has been suggested as biomarker for gastric cancers 44,45 . From symmetry with signature C6, patients with signature C8 might possibly benefit from ANO1 inhibitory therapy 36 .…”

Section: Discussionmentioning

confidence: 99%

Multi-omic signatures identify pan-cancer classes of tumors beyond tissue of origin

Gonzalez-Reymundez

Vázquez

2019

Preprint

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7Despite recent advances in treatment, cancer continues to be one of the most lethal human 8 maladies. One of the challenges of cancer treatment is the extreme diversity among seemingly 9 identical tumors: while some tumors may have good prognosis and are treatable, others are quite 10 aggressive, and may lack of effective therapies. Most of this variability comes from wide-spread 11 mutations and epigenetic alterations. Using a novel omic-integration method, we have exploited 12 this molecular information to re-classify tumors beyond the constraints of cell type. Eight novel 13 tumor groups (C1-8) emerged, characterized by unique cancer signatures. C3 had better prognosis, 14 genome stability, and immune infiltration. C2 and C5 had higher genome instability and poorer 15 clinical outcomes. Remaining clusters were characterized by worse outcomes, along with higher 16 genome instability. C1, C7, and C8 were upregulated for cellular and mitochondrial translation, 17 and relatively low proliferation. C6 and C4 were also downregulated for cellular and mitochondrial 18 translation, and had high proliferation rates. C4 was represented by copy losses on chromosome 19 6, and had the highest number of metastatic samples. C8 was characterized by copy losses on 20 chromosome 11, having also the lowest lymphocytic infiltration rate. C6 had the lowest natural 21 killer infiltration rate and was represented by copy gains of genes in chromosome 11. C7 was 22 represented by copy gains on chromosome 6, and had the highest upregulation in mitochondrial 23 translation. We believe that, since molecularly alike tumors could respond similarly to treatment, 24 our results could inform therapeutic action. 25 Significance 26 Cancer has been traditionally studied as a family of different diseases from different anatomical 27 sites. Nevertheless, regardless of the tissue of origin, cancer can be characterized by molecular 28 alterations on mechanisms controlling cell fate and progression. In this study, we integrate 33 29 cancer types and show the existence of eight clusters with unique genomic signatures and clinical 30 characteristics, beyond the site of origin of the tumor. The study and treatment of cancer, based on 31 predominant molecular features, rather than site of origin, can potentially aid in the discovery of 32 novel therapeutic alternatives.33

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Mitochondrial ribosomes in cancer

Cited by 137 publications

References 166 publications

AMPK: Potential Therapeutic Target for Ischemic Stroke

AMPK: Potential Therapeutic Target for Ischemic Stroke

DHX30 coordinates cytoplasmic translation and mitochondrial function contributing to cancer cell survival

Multi-omic signatures identify pan-cancer classes of tumors beyond tissue of origin

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