Mitochondrial fusion/fission and autophagy in endoplasmic reticulum (ER), mitochondria, and mitochondria-associated ER membranes (MAMs). (IMAGE)

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Mitochondrial fusion/fission and autophagy in endoplasmic reticulum (ER), mitochondria, and mitochondria-associated ER membranes (MAMs).

Caption

(A) Mitochondrial fusion/fission and autophagy in physiology. Dynamin-related protein 1 (DRP1), mitochondrial dynamics proteins of 49/51 kDa (MiD49/51), mitochondrial fission factor (MFF), and mitochondrial fission protein 1 (FIS1) encircle the scission sites, leading to mitochondrial fission. Mitochondrial fusion protein 2 (MFN2), mitoguardin, and optic atrophy protein 1 (OPA1) participate in mitochondrial fusion. Autophagy-related protein 14 (ATG14) and ATG5 recruit to the MAMs during mitochondrial autophagy. The interaction between FUN14 domain-containing 1 (FUNDC1) and DRP1 promotes mitochondrial division and mitophagy. MFN2, inositol 1,4,5-trisphosphate receptor (IP3R), and phosphofurin acidic cluster sorting protein 2 (PACS2) can interact with autophagy regulatory proteins to promote membrane structure recycling. Vesicle-associated membrane protein-associated protein B (VAPB)-protein tyrosine phosphatase interacting protein 51 (PTPI51) regulates mitochondrial autophagy by modulating the tethering. (B) Mitochondrial fusion/fission and mitophagy and therapy targets in colorectal cancer (CRC). Sodium butyrate (NaBt) down-regulates the expression of DRP1 and inhibits the progression of CRC. Down-regulation of MFN2 by miR-17-5p impairs mitochondrial fusion, ultimately leading to 5-fluorouracil resistance in CRC cells. In human CRC tissues, PTEN-induced putative kinase 1 (PINK1)/Parkin expression is down-regulated. δ-valerobetaine (δVB) and aloe gel glucomannan (AGP) induce mitochondrial apoptosis through the PINK1/Parkin mitophagy pathway. Tanshinone IIA (Tan IIA) promotes apoptosis in CRC cells by inhibiting Parkin-mediated mitochondrial autophagy. Cirsiliol inhibits CRC cell proliferation by disrupting mitochondrial morphology and reducing levels of mitophagy-related proteins, including PINK1, Parkin, and FUNDC1. The non-coding RNA piR-823 interacts with PINK1 to inhibit mitochondrial autophagy and cell apoptosis in CRC. The orange figure indicates overexpression. The blue figure indicates underexpression.

Credit

Lanshu Xiao, Yao Wei, Yiping Qin, Bianqin Guo

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