ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.
Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.
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The Mitochondrial Ribosome Dysfunction in Human Primary Alveolar Type II Cells in Emphysema
Session Title
TP109 - TP109 COPD AND E-CIGARETTES: PRE-CLINICAL MODELS AND MECHANISMS
Abstract
A4278 - The Mitochondrial Ribosome Dysfunction in Human Primary Alveolar Type II Cells in Emphysema
Author Block: K. Bahmed1, L. Karim1, G. J. Criner2, N. Marchetti3, S. Bolla1, R. P. Bowler4, B. Kosmider1; 1Thoracic Medicine and Surgery, Temple University, Philadelphia, PA, United States, 2Pulmonary & Critical Care Medicine, Temple University Hospital, Philadelphia, PA, United States, 3Pulmonary Division, Temple University Hospital, Philadelphia, PA, United States, 4National Jewish Health, Denver, CO, United States.
RATIONALE: Pulmonary emphysema is a progressive disease characterized by airspace enlargement and destruction of alveoli, consequently reducing the surface area available for gas exchange. Cigarette smoke is the main risk factor for this disease development. Oxidative phosphorylation complexes are composed of proteins encoded by mitochondrial and nuclear genomes. METHODS: We isolated alveolar type II (ATII) cells from control non-smokers and smokers and emphysema patients. ATII cells produce and secrete pulmonary surfactants and are abundant in mitochondria, which generate ATP for their function. RESULTS: We found a decrease in ND1 and UQCRC2 protein expression levels in ATII cells in emphysema, which are components of complex I and complex III, respectively. Moreover, nuclear NDUFS1 and SDHB protein levels were increased and mitochondrial transcribed ND1 protein expression was decreased. These results suggest an impairment of the nuclear and mitochondrial stoichiometry in emphysema. We also found low levels of the mitoribosome structural protein MRPL48 in ATII cells in this disease. Mitochondrial 12S and 16S rRNAs are required for the assembly of small and large subunits of mitoribosome, respectively. Our results show decreased 16S rRNA expression and increased 12S rRNA levels in ATII cells isolated from emphysema patients in comparison with control smokers. Moreover, we analyzed miR4485-3p levels, which originates from either nuclear DNA and also from mitochondrial MT-RNR2 gene transcripts. CONCLUSION: Our results suggest a negative feedback loop between miR-4485-3p and 16S rRNA. Obtained results provide molecular mechanisms of mitoribosome dysfunction in human primary ATII cells in emphysema.
Author Block: K. Bahmed1, L. Karim1, G. J. Criner2, N. Marchetti3, S. Bolla1, R. P. Bowler4, B. Kosmider1; 1Thoracic Medicine and Surgery, Temple University, Philadelphia, PA, United States, 2Pulmonary & Critical Care Medicine, Temple University Hospital, Philadelphia, PA, United States, 3Pulmonary Division, Temple University Hospital, Philadelphia, PA, United States, 4National Jewish Health, Denver, CO, United States.
RATIONALE: Pulmonary emphysema is a progressive disease characterized by airspace enlargement and destruction of alveoli, consequently reducing the surface area available for gas exchange. Cigarette smoke is the main risk factor for this disease development. Oxidative phosphorylation complexes are composed of proteins encoded by mitochondrial and nuclear genomes. METHODS: We isolated alveolar type II (ATII) cells from control non-smokers and smokers and emphysema patients. ATII cells produce and secrete pulmonary surfactants and are abundant in mitochondria, which generate ATP for their function. RESULTS: We found a decrease in ND1 and UQCRC2 protein expression levels in ATII cells in emphysema, which are components of complex I and complex III, respectively. Moreover, nuclear NDUFS1 and SDHB protein levels were increased and mitochondrial transcribed ND1 protein expression was decreased. These results suggest an impairment of the nuclear and mitochondrial stoichiometry in emphysema. We also found low levels of the mitoribosome structural protein MRPL48 in ATII cells in this disease. Mitochondrial 12S and 16S rRNAs are required for the assembly of small and large subunits of mitoribosome, respectively. Our results show decreased 16S rRNA expression and increased 12S rRNA levels in ATII cells isolated from emphysema patients in comparison with control smokers. Moreover, we analyzed miR4485-3p levels, which originates from either nuclear DNA and also from mitochondrial MT-RNR2 gene transcripts. CONCLUSION: Our results suggest a negative feedback loop between miR-4485-3p and 16S rRNA. Obtained results provide molecular mechanisms of mitoribosome dysfunction in human primary ATII cells in emphysema.
