2017
DOI: 10.1074/jbc.m117.809012
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Lactate-mediated mitoribosomal defects impair mitochondrial oxidative phosphorylation and promote hepatoma cell invasiveness

Abstract: Impaired mitochondrial oxidative phosphorylation (OXPHOS) capacity, accompanied by enhanced glycolysis, is a key metabolic feature of cancer cells, but its underlying mechanism remains unclear. Previously, we reported that human hepatoma cells that harbor OXPHOS defects exhibit high tumor cell invasiveness via elevated claudin-1 (CLN1). In the present study, we show that OXPHOS-defective hepatoma cells (SNU354 and SNU423 cell lines) exhibit reduced expression of mitochondrial ribosomal protein L13 (MRPL13), a … Show more

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Cited by 53 publications
(63 citation statements)
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References 40 publications
(43 reference statements)
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“…Moreover, exposure of oxidative hepatoma cells (Ch-L and SNU387) to lactate decreased OXPHOS activity in a rapid response via PDH phosphorylation. Recently, we reported that lactate also induced mitoribo-somal defect in a delayed response via suppressing MRPL13 expression, eventually contributing to the endogenous OXPHOS defect of SNU354 and SNU423 cells (46). Together, these results indicate that lactate may play a key role in the maintenance and propagation of mitochondrial OXPHOS dysfunction in the tumoral context, even under normoxic conditions.…”
Section: Ldhb Suppression Regulates Oxphos Via Lactate/pdk-pdh Axismentioning
confidence: 72%
“…Moreover, exposure of oxidative hepatoma cells (Ch-L and SNU387) to lactate decreased OXPHOS activity in a rapid response via PDH phosphorylation. Recently, we reported that lactate also induced mitoribo-somal defect in a delayed response via suppressing MRPL13 expression, eventually contributing to the endogenous OXPHOS defect of SNU354 and SNU423 cells (46). Together, these results indicate that lactate may play a key role in the maintenance and propagation of mitochondrial OXPHOS dysfunction in the tumoral context, even under normoxic conditions.…”
Section: Ldhb Suppression Regulates Oxphos Via Lactate/pdk-pdh Axismentioning
confidence: 72%
“…These hub RBPs are mitochondrial ribosomal proteins that are essential for maintaining mitochondrial functions. Impaired mitochondrial functions such as apoptosis and oxidative phosphorylation are found in most cancers, however, their mechanisms are unclear (Koc et al, 2015;Lee et al, 2017;Lin et al, 2019). Lee et al (2017) found that suppressed MRPL13 expression increased hepatoma cell invasiveness.…”
Section: Discussionmentioning
confidence: 99%
“…Impaired mitochondrial functions such as apoptosis and oxidative phosphorylation are found in most cancers, however, their mechanisms are unclear (Koc et al, 2015;Lee et al, 2017;Lin et al, 2019). Lee et al (2017) found that suppressed MRPL13 expression increased hepatoma cell invasiveness. Koc et al (2015) proposed that defects in mitochondrial function in head and neck squamous cell carcinoma might be caused by a decrease in MRPL11 expression.…”
Section: Discussionmentioning
confidence: 99%
“…The second network of genes encoding several mitochondrial ribosomal protein large (MRPL) was also identified by this analysis of downregulated genes. Seven of the eight genes encoded proteins involved in mitochondrial protein synthesis/ribosomes, and mitochondrial markers, including different MRPLs, which have recently been linked to carcinogenesis [ 35 , 36 ]. The last gene encoded a mitochondrial protein involved in energy metabolism.…”
Section: Resultsmentioning
confidence: 99%
“…Compensatory upregulation of this gene in response to NF-κB inhibition is probably consistent with this. Our network analysis also identified a network associated with NF-κB inhibition as well as altered expression of MRRPL , SNRP , and IFIT genes that possibly are involved in malignant cell transformation [ 35 , 36 , 37 , 38 ]. Of particular interest in the setting of AML is SNRP that is crucial for the spliceosome [ 37 ]; this effect may be relevant, especially for patients with mutations in spliceosome genes [ 4 ].…”
Section: Discussionmentioning
confidence: 99%