NADH dehydrogenase subunit 1/4/5 promotes survival of acute myeloid leukemia by mediating specific oxidative phosphorylation

Abstract

acute myeloid leukemia (aMl) is a type of hematological malignancy caused by uncontrolled clonal proliferation of hematopoietic stem cells. The special energy metabolism mode of aMl relying on oxidative phosphorylation is different from the traditional 'Warburg effect'. However, its mechanism is not clear. in the present study, it was demonstrated that the mrna expression levels of nadH dehydrogenase subunit 1, 4 and 5 (nd1, nd4 and nd5) were upregulated in aMl samples from The cancer Genome atlas database using the limma package in the r programming language. reverse transcription-quantitative Pcr and eliSa were used to verify the upregulation of nd1, nd4 and nd5 in clinical samples. Pan-cancer analysis revealed that the expression of nd1 was upregulated only in aMl, nd2 was upregulated only in aMl and thymoma, and nd4 was upregulated only in aMl and kidney chromophobe. in the present study, it was demonstrated that silencing of nd1/4/5 could inhibit the proliferation of aMl cells in transplanted tumor of nude mice. additionally, it was found that oxidative phosphorylation and energy metabolism of aMl cells were decreased after silencing of nd1/4/5. in conclusion, the present study suggested that nd1/4/5 may be involved in the regulation of oxidative phosphorylation metabolism in aMl as a potential cancer-promoting factor.

Analysis of Whole-Genome as a Novel Strategy for Animal Species Identification

“…Cn_target3 is located in the D-Loop region of mitochondrial DNA, and Ce_target3 is located in the gene-encoding NADH dehydrogenase subunit 1(ND1). Studies on the D-loop have centered around its involvement in telomere maintenance [ 32 ], DNA damage repair [ 33 ], and disease processes [ 34 , 35 , 36 ], while research on ND1 has primarily focused on its role in various cancer processes [ 35 , 37 ]. Apart from the aforementioned cases, we also found species-specific target sequences, including Rt_target3 located in the COI sequence, within common sequences utilized for identification purposes.…”

Mitochondrial complex I subunit MT-ND1 mutations affect disease progression

“…The expression level of MT-ND1 varies among tissues. The MT-ND1 protein level is high in the heart, brain, kidneys, liver, as well as in malignant tumors, such as myeloid leukemia, thyroid cancer, and early pancreatic ductal adenocarcinoma (PDAC) [ [7] , [8] , [9] ]. Functionally, MT-ND1 is a potential testosterone target, and lack of testosterone leads to downregulation of MT-ND1 expression, reduction of complex I activity, damage to mitochondrial function, oxidative damage to the substantia nigra striatum, and damage to the dopaminergic system [ 10 ].…”

“…In addition, there is a heteroplasmy phenomenon in which harmful mutations coexist with normal mtDNA molecules [ 12 , 13 ]. Previous studies have shown that MT-ND1 has mutations in Leber hereditary optic neuropathy (LHON) disease, diabetes, malignant tumors, and other diseases, and its mutations affect the body's pathophysiological processes [ 8 , [14] , [15] , [16] ].…”

POLR3A-mutated Wiedemann-Rautenstrauch fibroblasts display differential profile of intron retention and expression of TP53 isoforms

“…The NADH dehydrogenase complex or complex I is the first enzyme in the electron transport chain, and it catalyzes electron transfer from NADH to ubiquinone. This suggests that there may be a deficiency in energy generation in WRS cells [17].…”