Abstract
Abstract Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria. Mieap suppresses murine intestinal tumor via its mitochondrial quality control (1). Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer (2). To explore the role of the Mieap-regulated mitochondria quality control function in human colorectal cancer tissues, we examined the Mieap expression in primary colorectal cancer tissues by performing immunohistochemical analysis with anti-human Mieap antibody. Mieap expression was very low in normal colorectal epithelial cells, whereas the strong expression of the Mieap protein was detected in the hypoxic cell death regions of colorectal adenoma and adenocarcinoma, suggesting the role of Mieap in hypoxic cell death. Overexpression of Mieap in vitro induced large vacuole structures (MIV: Mieap-induced vacuole) in HCT116 colorectal cancer cells (Mieap-deficient colorectal cancer cells). MIV engulfed and degraded unhealthy mitochondria, leading to caspase-dependent cancer cell death. Re-expression of Mieap in HCT116 cells resulted in striking suppression of tumor growth in vivo. These results suggest that Mieap plays a critical role in hypoxic tumor cell death via lysosomal degradation of unhealthy mitochondria. (1) Tsuneki et al. Mieap suppresses murine intestinal tumor via its mitochondrial quality control. Sci. Rep. 5: 12472 (2015). (2) Kamino et al. Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer. Oncogenesis 5: e181 (2016). Citation Format: Yasuyuki Nakamura, Masayuki Tsuneki, Makoto Yamamoto, Hirofumi Arakawa. Mieap, the mitochondria-eating protein, induces cell death by eating unhealthy mitochondria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3316. doi:10.1158/1538-7445.AM2017-3316
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