Mitochondrial transcription factor A (TFAM) is essential for the replication, transcription and maintenance of mitochondrial DNA (mtDNA). The role of TFAM in non-small cell lung cancer (NSCLC) remains largely unknown. Herein, we report that downregulation of TFAM in NSCLC cells resulted in cell cycle arrest at G1 phase and significantly blocked NSCLC cell growth and migration through the activation of reactive oxygen species (ROS)-induced c-Jun amino-terminal kinase(JNK)/p38 MAPK signaling and decreased cellular bioenergetics. We further found that TFAM downregulation in NSCLC cells led to increased apoptotic cell death and enhanced the sensitivity of NSCLC cells to cisplatin. Tissue microarray (TMA) data showed that elevated expression of TFAM was related to the histological grade and TNM stage of NSCLC patients. We also demonstrated that TFAM is an independent prognostic factor for overall survival of NSCLC patients. Taken together, our findings suggest that TFAM could serve as a potential diagnostic biomarker and molecular target for the treatment of NSCLC, as well as for prediction of the effectiveness of chemotherapy.

No abstract

The natural small molecule compound: 2,3,5,6-tetramethylpyrazine (TMP), is a major component of the Chinese medicine Chuanxiong, which has wide clinical applications in dilating blood vessels, inhibiting platelet aggregation and treating thrombosis. Recent work suggests that TMP is also an antitumour agent. Despite its chemotherapeutic potential, the mechanism(s) underlying TMP action are unknown. Herein, we demonstrate that TMP binds to mitochondrial transcription factor A (TFAM) and blocks its degradation by the mitochondrial Lon protease. TFAM is a key regulator of mtDNA replication, transcription and transmission. Our previous work showed that when TFAM is not bound to DNA, it is rapidly degraded by the ATP-dependent Lon protease, which is essential for mitochondrial proteostasis. In cultured cells, TMP specifically blocks Lon-mediated degradation of TFAM, leading to TFAM accumulation and subsequent up-regulation of mtDNA content in cells with substantially low levels of mtDNA. In vitro protease assays show that TMP does not directly inhibit mitochondrial Lon, rather interacts with TFAM and blocks degradation. Pull-down assays show that biotinylated TMP interacts with TFAM. These findings suggest a novel mechanism whereby TMP stabilizes TFAM and confers resistance to Lon-mediated degradation, thereby promoting mtDNA up-regulation in cells with low mtDNA content.

Lithium ore deposits are divided into pegmatite and brine deposits. The Puna Plateau and the Qinghai–Tibetan Plateau (QTP) are home to the most abundant brine lithium deposits worldwide. Very few studies have investigated the chronology of brine lithium deposits. This paper reports the Optically Stimulated Luminescence (OSL) dating measurements for typical brine lithium deposits at QTP, including East Taijnar Salt Lake, West Taijnar Salt Lake, and Yiliping Salt Lake in the central Qaidam Basin. Combining the results of OSL dating with previous studies and mineral composition obtained by X-ray diffraction analysis (XRD), this study summarizes the age and characteristics of the climatic environment during the formation of brine lithium deposits in the Qaidam Basin. The main results are: 1) Brine lithium deposits in the Qaidam Basin began to form since 40 ka. Brine lithium deposits in South America formed during the middle Pleistocene and late Pleistocene, and are older than the deposits in the Qaidam Basin. The lithium deposits of Tibet formed around 4 ka, are the youngest. 2) The climate in East Taijnar Salt Lake and West Taijnar Salt Lake was extremely cold and dry during 27–4.6 ka, with a relatively humid climatic condition at ∼10 ka. After 4.6 ka, the environment was comparatively more humid around both lakes. Yiliping Salt Lake had a dry climate since 38.09 ka, and the climate in the Three Lakes area is mainly controlled by the westerlies in the Holocene; and 3) East Taijnar Salt Lake, West Taijnar Salt Lake and Yiliping Salt Lake were located in the same secondary basin during the late Pleistocene. However, tectonic activity around 40 ka led to the evolution of Yiliping Salt Lake into an independent basin. East Taijnar Salt Lake and West Taijnar Salt Lake separated around 27 ka, and then deposited the lower salt layers until the Holocene. The substantial amount of detrital minerals that the Nalinggele River brought during the Holocene led to a brief desalination of East Taijnar Salt Lake. The upper salt layer was deposited in East Taijnar Salt Lake and West Taijnar Salt Lake during this period due to the extremely dry climate.