Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics

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.