The ribosome filter hypothesis posits that ribosomes are not simple non-selective translation machines but may also function as regulatory elements in protein synthesis. Recent data supporting ribosomal filtering come from plant mitochondria where it has been shown that translation of mitochondrial transcripts encoding components of oxidative phosphorylation complexes (OXPHOS) and of mitoribosomes can be differentially affected by alterations in mitoribosomes. The biogenesis of mitoribosome was perturbed by silencing of a gene encoding a small-subunit protein of the mitoribosome in Arabidopsis thaliana. As a consequence, the mitochondrial OXPHOS and ribosomal transcripts were both upregulated, but only the ribosomal proteins were oversynthesized, while the OXPHOS subunits were actually depleted. This finding implies that the heterogeneity of plant mitoribosomes found in vivo could contribute to the functional selectivity of translation under distinct conditions. Furthermore, global analysis indicates that biogenesis of OXPHOS complexes in plants can be regulated at different levels of mitochondrial and nuclear gene expression, however, the ultimate coordination of genome expression occurs at the complex assembly level.
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http://dx.doi.org/10.3389/fpls.2014.00079 | DOI Listing |
J Immunother Cancer
January 2025
Biotherapy Center & Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
Background: Glucose deprivation inhibits T-cell metabolism and function. Glucose levels are low in the tumor microenvironment of solid tumors and insufficient glucose uptake limits the antitumor response of T cells. Furthermore, glucose restriction can contribute to the failure of chimeric antigen receptor T (CAR-T) cell therapy for solid tumors.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-Di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
Bioenergetic therapy based on tumor glucose metabolism is emerging as a promising therapeutic modality. To overcome the poor bioavailability and toxicity of arenobufagin (ArBu), a MOF-derived intelligent nanosystem, ZIAMH, was designed to facilitate energy deprivation by simultaneous interventions of glycolysis, OXPHOS and TCA cycle. Herein, zeolitic imidazolate framework-8 was loaded with ArBu and indocyanine green, encapsulated within metal-phenolic networks for chemodynamic therapy and hyaluronic acid modification for tumor targeting.
View Article and Find Full Text PDFCell Death Dis
January 2025
Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Mitochondrial oxidative phosphorylation (OXPHOS) is a therapeutic vulnerability in glycolysis-deficient cancers. Here we show that inhibiting OXPHOS similarly suppresses the proliferation and tumorigenicity of glycolytically competent colorectal cancer (CRC) cells in vitro and in patient-derived CRC xenografts. While the increased glycolytic activity rapidly replenished the ATP pool, it did not restore the reduced production of aspartate upon OXPHOS inhibition.
View Article and Find Full Text PDFMol Med
January 2025
Association for Systems Science, Via S. Stefano, 42, I-75100, Matera, Italy.
The Systemic Evolutionary Theory of the Origin of Cancer (SETOC) is a recently proposed theory founded on two primary principles: the cooperative and endosymbiotic process of cell evolution as described by Lynn Margulis, and the integration of complex systems operating in eukaryotic cells, which is a core concept in systems biology. The SETOC proposes that malignant transformation occurs when cells undergo a continuous adaptation process in response to long-term injuries, leading to tissue remodeling, chronic inflammation, fibrosis, and ultimately cancer. This process involves a maladaptive response, wherein the 'endosymbiotic contract' between the nuclear-cytoplasmic system (derived from the primordial archaeal cell) and the mitochondrial system (derived from the primordial α-proteobacterium) gradually breaks down.
View Article and Find Full Text PDFEMBO J
January 2025
Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
Mitochondrial metabolism requires the chaperoned import of disulfide-stabilized proteins via CHCHD4/MIA40 and its enigmatic interaction with oxidoreductase Apoptosis-inducing factor (AIF). By crystallizing human CHCHD4's AIF-interaction domain with an activated AIF dimer, we uncover how NADH allosterically configures AIF to anchor CHCHD4's β-hairpin and histidine-helix motifs to the inner mitochondrial membrane. The structure further reveals a similarity between the AIF-interaction domain and recognition sequences of CHCHD4 substrates.
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