A549 cells contain enlarged mitochondria with independently functional clustered mtDNA nucleoids
| Autor: | Miguel Garcia-Diaz, Daniel F. Bogenhagen, Aleksandrs Nasonovs |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Physiology
Molecular biology Glutamine Respiratory chain Mitochondrion Mitochondrial Dynamics Biochemistry Transforming Growth Factor beta Transcription (biology) Mitochondrial ribosome Amino Acids RNA structure Energy-Producing Organelles Membrane Potential Mitochondrial Staining Microscopy Confocal Multidisciplinary Organic Compounds Acidic Amino Acids Monosaccharides Mitochondrial DNA Mitochondria Cell biology Nucleic acids Electrophysiology Membrane Staining Chemistry Mitochondrial Membranes Physical Sciences Medicine Cellular Structures and Organelles Research Article Forms of DNA Science Carbohydrates Bioenergetics Biology Research and Analysis Methods DNA Mitochondrial Membrane Potential Electron Transport Complex IV Organelle Genetics Humans Nucleoid A549 cell Organic Chemistry Chemical Compounds Biology and Life Sciences Proteins Cell Biology DNA Macromolecular structure analysis Glucose A549 Cells Specimen Preparation and Treatment RNA |
| Zdroj: | PLoS ONE PLoS ONE, Vol 16, Iss 3, p e0249047 (2021) |
| ISSN: | 1932-6203 |
| Popis: | Mitochondria are commonly viewed as highly elongated organelles with regularly spaced mtDNA genomes organized as compact nucleoids that generate the local transcripts essential for production of mitochondrial ribosomes and key components of the respiratory chain. In contrast, A549 human lung carcinoma cells frequently contain apparently swollen mitochondria harboring multiple discrete mtDNA nucleoids and RNA processing granules in a contiguous matrix compartment. While this seemingly aberrant mitochondrial morphology is akin to “mito-bulbs” previously described in cells exposed to a variety of genomic stressors, it occurs in A549 cells under typical culture conditions. We provide a detailed confocal and super-resolution microscopic investigation of the incidence of such mito-bulbs in A549 cells. Most mito-bulbs appear stable, engage in active replication and transcription, and maintain respiration but feature an elevated oxidative environment. High concentrations of glucose and/or L-glutamine in growth media promote a greater incidence of mito-bulbs. Furthermore, we demonstrate that treatment of A549 cells with TGFβ suppresses the formation of mito-bulbs while treatment with a specific TGFβ pathway inhibitor substantially increases incidence. This striking heterogeneity of mitochondrial form and function may play an important role in a variety of diseases involving mitochondrial dysfunction. |
| Databáze: | OpenAIRE |
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