HIF-1α regulates COXIV subunits, a potential mechanism of self-protective response to microwave induced mitochondrial damages in neurons

Abstract

Anxiety and speculation about potential health hazards of microwaves exposure are spreading in the past decades. Hypoxia-inducible factor-1α (HIF-1α), which can be activated by reactive oxygen species (ROS), played pivotal roles in protective responses against microwave in neuron-like cells. In this study, we established 30 mW/cm2 microwave exposed animal model, which could result in revisable injuries of neuronal mitochondria, including ultrastructure and functions, such as ROS generation and cytochrome c oxidase (COX) activity. We found that the ratio of COXIV-1/COXIV-2, two isoforms of COXIV, decreased at 1 d and increased from 3 d to 14 d. Similar expression changes of HIF-1α suggested that COXIV-1 and COXIV-2 might be regulated by HIF-1α. In neuron-like cells, 30 mW/cm2 microwave down-regulated COX activity from 30 min to 6 h, and then started to recover. And, both HIF-1α transcriptional activity and COXIV-1/COXIV-2 ratio were up-regulated at 6 h and 9 h after exposure. Moreover, HIF-1α inhibition down-regulated COXIV-1 expression, promoted ROS generation, impaired mitochondrial membrane potentials (MMP), as well as abolished microwave induced ATP production. In conclusion, microwave induced mitochondrial ROS production activated HIF-1α and regulated COXIV-1 expression to restore mitochondria functions. Therefore, HIF-1α might be a potential target to impair microwave induced injuries.

MiR-30a-5p Downregulation Induces Neuronal Autophagy by Activating AMPK After 2856MHz Microwave Radiation

“…Through bioinformatics analysis, we predicted the target genes of miR-30a that may be involved in autophagy regulation, including Beclin1, Prkaa2, Irs1, Pik3r2, Rras2, Ddit4, Gabarapl2 and Atg12. The results of our previous study demonstrated that microwave radiation induces abnormal energy metabolism in hippocampal neurons and neuron-like cells [30,31]. In the present study, we showed that microwave radiation activates AMPK signaling, acellular energy sensor, in both rat hippocampi and neuron-like cells.…”

“…4C). We previously showed that microwave radiation can induce abnormal energy metabolism in hippocampal neurons and neuron-like cells [30,31].…”

Quality control of the mitochondrion

“…Furthermore, it is required for the maturation of several proteins involved in mitochondrial gene expression (SLIRP, MTERFD3 and FASTKD2), mtDNA replication (SSBP) and the ATP-dependent mitoprotease CLPX (Zurita Rendón andShoubridge, 2018, Lagouge et al, 2015) (Figure 3, mtDNA expression). Finally, it degrades COX4-1 under hypoxic conditions to promote the assembly of COX4-2, a structural subunit of the terminal electron transport chain (ETC) enzyme cytochrome c oxidase, thereby optimizing electron transfer and oxygen consumption (Hao et al, 2018) (Figure 3, OXPHOS complexes). Given the crucial role of LONP1 in mitochondrial function, it is not surprising that patients harboring mutations in LONP1 exhibit OXPHOS deficiencies observed in other mitochondrial diseases (Peter et al, 2018).…”

Molybdenum and Cadmium Co-induce Mitochondrial Quality Control Disorder via FUNDC1-Mediated Mitophagy in Sheep Kidney

“…Moreover, the transformation of LC3 from LC3I to LC3II is the pivotal step of mitophagosome formation, and LC3II content reflects straightway the amount of mitophagosomes (50). Cytochrome c oxidase (COX) subunits, complex IV in the mitochondrial respiratory chain, are located in the inner mitochondrial membrane (51). In our research, treatment with Mo and/or Cd enhanced the co-localization of COX IV-labeled mitochondria with LC3.…”