Mitochondrial Ribosome Dysfunction in Human Alveolar Type II Cells in Emphysema

Loukmane Karim, Chih Ru Lin, Beata Kosmider, Gerard Criner, Nathaniel Marchetti, Sudhir Bolla, Russell Bowler, Karim Bahmed

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Pulmonary emphysema is characterized by airspace enlargement and the destruction of alveoli. Alveolar type II (ATII) cells are very abundant in mitochondria. OXPHOS complexes are composed of proteins encoded by the mitochondrial and nuclear genomes. Mitochondrial 12S and 16S rRNAs are required to assemble the small and large subunits of the mitoribosome, respectively. We aimed to determine the mechanism of mitoribosome dysfunction in ATII cells in emphysema. ATII cells were isolated from control nonsmokers and smokers, and emphysema patients. Mito-chondrial transcription and translation were analyzed. We also determined the miRNA expression. Decreases in ND1 and UQCRC2 expression levels were found in ATII cells in emphysema. Moreo-ver, nuclear NDUFS1 and SDHB levels increased, and mitochondrial transcribed ND1 protein expression decreased. These results suggest an impairment of the nuclear and mitochondrial stoichi-ometry in this disease. We also detected low levels of the mitoribosome structural protein MRPL48 in ATII cells in emphysema. Decreased 16S rRNA expression and increased 12S rRNA levels were observed. Moreover, we analyzed miR4485-3p levels in this disease. Our results suggest a negative feedback loop between miR-4485-3p and 16S rRNA. The obtained results provide molecular mechanisms of mitoribosome dysfunction in ATII cells in emphysema.

Original languageEnglish
Article number1497
JournalBiomedicines
Volume10
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • alveolar type II cells
  • emphysema
  • lung
  • mitochondria
  • mitoribosome

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