G-Quadruplex Dynamics Contribute To Regulation Of Mitochondrial Gene Expression

Single-stranded DNA or RNA sequences rich in guanine (G) can adopt non-canonical structures known as G-quadruplexes (G4). Mitochondrial DNA (mtDNA) sequences that are predicted to form G4 are enriched on the heavy-strand and have been associated with formation of deletion breakpoints. Increasing evidence supports the ability of mtDNA to form G4 in cancer cells; however, the functional roles of G4 structures in regulating mitochondrial nucleic acid homeostasis in non-cancerous cells remain unclear. Here, we demonstrate by live cell imaging that the G4-ligand RHPS4 localizes primarily to mitochondria at low doses. We find that low doses of RHPS4 do not induce a nuclear DNA damage response but do cause an acute inhibition of mitochondrial transcript elongation, leading to respiratory complex depletion. We also observe that RHPS4 interferes with mtDNA levels or synthesis both in cells and isolated mitochondria. Importantly, a mtDNA variant that increases G4 stability and anti-parallel G4-forming character shows a stronger respiratory defect in response to RHPS4, supporting the conclusion that mitochondrial sensitivity to RHPS4 is G4-mediated. Taken together, our results indicate a direct role for G4 perturbation in mitochondrial genome replication, transcription processivity, and respiratory function in normal cells

Dissipative and Non-dissipative Single-Qubit Channels: Dynamics and Geometry

Single-qubit channels are studied under two broad classes: amplitude damping channels and generalized depolarizing channels. A canonical derivation of the Kraus representation of the former, via the Choi isomorphism is presented for the general case of a system's interaction with a squeezed thermal bath. This isomorphism is also used to characterize the difference in the geometry and rank of these channel classes. Under the isomorphism, the degree of decoherence is quantified according to the mixedness or separability of the Choi matrix. Whereas the latter channels form a 3-simplex, the former channels do not form a convex set as seen from an ab initio perspective. Further, where the rank of generalized depolarizing channels can be any positive integer upto 4, that of amplitude damping ones is either 2 or 4. Various channel performance parameters are used to bring out the different influences of temperature and squeezing in dissipative channels. In particular, a noise range is identified where the distinguishability of states improves inspite of increasing decoherence due to environmental squeezing.Comment: 12 pages, 4 figure