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The mitochondrial genome transcribes 13 mRNAs encoding proteins necessary for oxidative phosphorylation.
2024年5月3日，中国科学院广州生物医药与健康研究院刘兴国团队在 Cell Metabolism 在线发表题为“A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development”的研究论文，该研究细胞色素b (CYTB)是复合体III中唯一一个线粒体DNA编码的转录物，它也使用细胞质核糖体的标准遗传密码而不是线粒体遗传密码编码一个未被识别的187个氨基酸长的蛋白CYTB- 187AA。
After verifying the presence of this mtDNA-encoded protein produced by cytoplasmic translation (mPACT) using mass spectrometry and antibodies, it was found that CYTB-187AA predominantly localizes in the mitochondrial matrix and regulates ATP production by interacting with solute carrier family 25 member 3 (SLC25A3), thereby promoting pluripotent states from initiation to initial transition. A transgenic knock-in mouse model of CYTB-187AA silence was further established, and it was found that the reduction of CYTB-187AA impaired the fertility of females by reducing the number of ovarian follicles. In conclusion, this study is the first to discover a novel mPACT pattern of mitochondrial mRNA and demonstrate the physiological function of the 14th protein encoded by mtDNA.
Mitochondria are multifunctional organelles that provide energy for a wide variety of cellular activities, but are also indispensable in the regulation of apoptosis, cell signaling, and many biosynthetic pathways. Many of these functions require the release of substances from within the mitochondria into the cytoplasm or nucleus. As signaling molecules, mitochondrial reactive oxygen species (ROS) and Ca2+ are released into the cytoplasm and are involved in many processes such as apoptosis and cell fate. Mitochondrial apoptotic factors such as cytochrome c and AIF (apoptosis-inducing factors) are also released into the cytoplasm, triggering caspase activation or caspase-independent death pathways. As second messengers, mitochondrial metabolites are transferred to the cytoplasm and subsequently trigger profound genetic alterations. There have been some reports of mitochondrial DNA (mtDNA)-derived RNA and peptide release. Mitochondria-encoded peptides include MOTS-c, humanin, and small human peptides (SHLPs), which regulate adaptive responses to metabolic stress and are involved in a variety of biological processes. Mitochondrial non-coding RNAs, such as sensory non-coding mitochondrial RNAs (sncmtRNAs), long intergenic noncoding RNAs predicting cardiac remodeling (LIPCAR), long non-coding RNA cytochrome B (LncCYTB), and rRNAs, are exported from mitochondria and are associated with various physiological and pathological processes, including cancer, heart failure, aging, and early embryogenesis. MtDNA released into the cytoplasm or circulation triggers an immune response by activating innate immune receptors.
模式图（Credit: Cell Metabolism）
The mitochondrial genome is generally considered to contain 37 genes, of which 13 genes encode proteins, 22 genes encode transfer RNAs (tRNA), and 2 genes encode ribosomal RNAs (12S and 16S RNAs). That is, the standard isoleucine encodes ATA, which encodes methionine in mitochondria, arginine encodes AGA and AGG as stop codons, and the stop codon TGA encodes tryptophan. However, the possibility of cytoplasmic ribosomal translation of 13 mitochondrial genes encoding mRNAs has not yet been recognized or explored. The study describes cytochrome b (CYTB), the only mtDNA coding component in complex III, encoding a new 187 amino acids, mitochondrial localization protein (CYTB187AA), which is translated in the cytoplasm using the standard genetic code, revealing a novel mtDNA-encoded protein generated by the cytoplasmic translation (mPACT) pattern. The study further demonstrated that CYTB-187AA plays an important role in early mammalian development. This study is the first to discover a novel mPACT pattern of mitochondrial mRNA and demonstrates the physiological function of the 14th protein encoded by mtDNA.
Original link https://doi.org/10.1016/j.cmet.2024.04.012
Editor-in-charge|Explore Jun
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文章来源|“ iNature”
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