Abstract

Alveolar epithelial type II (AETII) cells are important for lung epithelium maintenance and function. We demonstrate that AETII cells from mouse lungs exposed to cigarette smoke (CS) increase the levels of the mitochondria-encoded non-coding RNA, mito-RNA-805, generated by the control region of the mitochondrial genome. The protective effects of mito-ncR-805 are associated with positive regulation of mitochondrial energy metabolism, and respiration. Levels of mito-ncR-805 do not relate to steady-state transcription or replication of the mitochondrial genome. Instead, CS-exposure causes the redistribution of mito-ncR-805 from mitochondria to the nucleus, which correlated with the increased expression of nuclear-encoded genes involved in mitochondrial function. These studies reveal an unrecognized mitochondria stress associated retrograde signaling, and put forward the idea that mito-ncRNA-805 represents a subtype of small non coding RNAs that are regulated in a tissue- or cell-type specific manner to protect cells under physiological stress.

Blumental-Perry et al. find that exposure to cigarette smoke causes the redistribution of the mitochondria-encoded non-codling RNA, mito-ncR-805, from mitochondria to the nucleus in alveolar epithelial cells. This relocation event correlates with increased expression of nuclear genes involved in mitochondrial function, suggesting that this response has a protective role.

Details

Title
Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics
Author
Blumental-Perry, A 1   VIAFID ORCID Logo  ; Jobava, R 2 ; Bederman, I 2 ; Degar, A J 3 ; Kenche, H 4 ; Guan, B J 2 ; Pandit, K 5 ; Perry, N A 2 ; Molyneaux, N D 2 ; Wu J 2 ; Prendergas, E 2 ; Z-W, Ye 6 ; Zhang, J 6 ; Nelson, C E 7   VIAFID ORCID Logo  ; Ahangari, F 8 ; Krokowski, D 9 ; Guttentag, S H 10 ; Linden, P A 11 ; Townsend, D M 12 ; Miron, A 2 ; M-J, Kang 8   VIAFID ORCID Logo  ; Kaminski, N 8   VIAFID ORCID Logo  ; Perry, Y 13 ; Hatzoglou, M 2   VIAFID ORCID Logo 

 University at Buffalo, State University of New York, Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887) 
 Case Western Reserve University, Department of Genetics and Genome Sciences, School of Medicine, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847) 
 Mercer University, College of Pharmacology, Atlanta, USA (GRID:grid.259906.1) (ISNI:0000 0001 2162 9738) 
 Mercer University School of Medicine, Savannah Campus, Biomedical Sciences, Savannah, USA (GRID:grid.259907.0); Savannah State University, Savannah, USA (GRID:grid.263219.d) (ISNI:0000 0004 0395 1215) 
 Sekusui XenoTech, LLC, Kansas City, USA (GRID:grid.422828.6) (ISNI:0000 0004 1798 670X) 
 Medical University of South Carolina, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
 Mercer University School of Medicine, Savannah Campus, Biomedical Sciences, Savannah, USA (GRID:grid.259907.0) 
 Yale School of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, and Center for RNA Science and Medicine, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
 Maria Curie-Skłodowska University, Department of Molecular Biology, Lublin, Poland (GRID:grid.29328.32) (ISNI:0000 0004 1937 1303) 
10  Vanderbilt University School of Medicine, Division of Neonatology, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
11  Case Western Reserve University School of Medicine, Department of Surgery, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847); University Hospitals Cleveland Medical Center, Cleveland, USA (GRID:grid.443867.a) (ISNI:0000 0000 9149 4843) 
12  Medical University of South Carolina, College of Pharmacy, Drug Discovery & Biomedical Sciences, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
13  University at Buffalo, State University of New York, Division of Thoracic Surgery, Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2471529169
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.