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      Abnormal Expression of Mitochondrial Ribosomal Proteins and Their Encoding Genes with Cell Apoptosis and Diseases

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          Abstract

          Mammalian mitochondrial ribosomes translate 13 proteins encoded by mitochondrial genes, all of which play roles in the mitochondrial respiratory chain. After a long period of reconstruction, mitochondrial ribosomes are the most protein-rich ribosomes. Mitochondrial ribosomal proteins (MRPs) are encoded by nuclear genes, synthesized in the cytoplasm and then, transported to the mitochondria to be assembled into mitochondrial ribosomes. MRPs not only play a role in mitochondrial oxidative phosphorylation (OXPHOS). Moreover, they participate in the regulation of cell state as apoptosis inducing factors. Abnormal expressions of MRPs will lead to mitochondrial metabolism disorder, cell dysfunction, etc. Many researches have demonstrated the abnormal expression of MRPs in various tumors. This paper reviews the basic structure of mitochondrial ribosome, focuses on the structure and function of MRPs, and their relationships with cell apoptosis and diseases. It provides a reference for the study of the function of MRPs and the disease diagnosis and treatment.

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          Most cited references133

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          Ribosome. The structure of the human mitochondrial ribosome.

          The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes. We have determined the structure of the intact mitoribosome to 3.5 angstrom resolution by means of single-particle electron cryogenic microscopy. It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules. The head domain of the small subunit, particularly the messenger (mRNA) channel, is highly remodeled. Many intersubunit bridges are specific to the mitoribosome, which adopts conformations involving ratcheting or rolling of the small subunit that are distinct from those seen in bacteria or eukaryotes. An intrinsic guanosine triphosphatase mediates a contact between the head and central protuberance. The structure provides a reference for analysis of mutations that cause severe pathologies and for future drug design. Copyright © 2015, American Association for the Advancement of Science.
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            Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the mitochondrial cristae.

            We used electron cryotomography of mitochondrial membranes from wild-type and mutant Saccharomyces cerevisiae to investigate the structure and organization of ATP synthase dimers in situ. Subtomogram averaging of the dimers to 3.7 nm resolution revealed a V-shaped structure of twofold symmetry, with an angle of 86° between monomers. The central and peripheral stalks are well resolved. The monomers interact within the membrane at the base of the peripheral stalks. In wild-type mitochondria ATP synthase dimers are found in rows along the highly curved cristae ridges, and appear to be crucial for membrane morphology. Strains deficient in the dimer-specific subunits e and g or the first transmembrane helix of subunit 4 lack both dimers and lamellar cristae. Instead, cristae are either absent or balloon-shaped, with ATP synthase monomers distributed randomly in the membrane. Computer simulations indicate that isolated dimers induce a plastic deformation in the lipid bilayer, which is partially relieved by their side-by-side association. We propose that the assembly of ATP synthase dimer rows is driven by the reduction in the membrane elastic energy, rather than by direct protein contacts, and that the dimer rows enable the formation of highly curved ridges in mitochondrial cristae.
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              Ribosome. The complete structure of the 55S mammalian mitochondrial ribosome.

              Mammalian mitochondrial ribosomes (mitoribosomes) synthesize mitochondrially encoded membrane proteins that are critical for mitochondrial function. Here we present the complete atomic structure of the porcine 55S mitoribosome at 3.8 angstrom resolution by cryo-electron microscopy and chemical cross-linking/mass spectrometry. The structure of the 28S subunit in the complex was resolved at 3.6 angstrom resolution by focused alignment, which allowed building of a detailed atomic structure including all of its 15 mitoribosomal-specific proteins. The structure reveals the intersubunit contacts in the 55S mitoribosome, the molecular architecture of the mitoribosomal messenger RNA (mRNA) binding channel and its interaction with transfer RNAs, and provides insight into the highly specialized mechanism of mRNA recruitment to the 28S subunit. Furthermore, the structure contributes to a mechanistic understanding of aminoglycoside ototoxicity.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                23 November 2020
                November 2020
                : 21
                : 22
                : 8879
                Affiliations
                [1 ]Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; huangguomin@ 123456impcas.ac.cn (G.H.); lihy@ 123456impcas.ac.cn (H.L.)
                [2 ]Advanced Energy Science and Technology Guangdong Laboratory, Huizhou 516029, China
                [3 ]Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China
                [4 ]College of Life Sciences, University of Chinese Academy of Sciences, Beijing 101408, China
                [5 ]School of Nuclear Science and Technology, University of Chinese Academy of Sciences, Beijing 101408, China
                Author notes
                [* ]Correspondence: zhangh@ 123456impcas.ac.cn ; Tel.: +86-0931-4969344
                [†]

                Contributed equally to this work.

                Article
                ijms-21-08879
                10.3390/ijms21228879
                7700125
                33238645
                4a7ad539-a56c-4bd4-b85b-d0fd189f66e7
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 October 2020
                : 17 November 2020
                Categories
                Review

                Molecular biology
                mitochondrial ribosome,mitochondrial ribosomal proteins,apoptosis,cancer,mitochondrial disease,biomarker

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