Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

Caterina Vianello; Veronica Cocetta; Daniela Catanzaro; Gerald W. Dorn; Angelo De Milito; Flavio Rizzolio; Vincenzo Canzonieri; Erika Cecchin; Rossana Roncato; Giuseppe Toffoli; Vincenzo Quagliariello; Annabella Di Mauro; Simona Losito; Nicola Maurea; Scaffa Cono; Gabriele Sales; Luca Scorrano; Marta Giacomello; Monica Montopoli

doi:10.1038/s41419-022-04741-9

Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

Caterina Vianello, Veronica Cocetta, Daniela Catanzaro, Gerald W. Dorn, Angelo De Milito, Flavio Rizzolio, Vincenzo Canzonieri, Erika Cecchin, Rossana Roncato, Giuseppe Toffoli, Vincenzo Quagliariello, Annabella Di Mauro, Simona Losito, Nicola Maurea, Scaffa Cono, Gabriele Sales, Luca Scorrano, Marta Giacomello, Monica Montopoli

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Abstract

Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.

Original language	English
Article number	398
Journal	Cell Death and Disease
Volume	13
Issue number	4
DOIs	https://doi.org/10.1038/s41419-022-04741-9
State	Published - Apr 2022

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Vianello, C., Cocetta, V., Catanzaro, D., Dorn, G. W., De Milito, A., Rizzolio, F., Canzonieri, V., Cecchin, E., Roncato, R., Toffoli, G., Quagliariello, V., Di Mauro, A., Losito, S., Maurea, N., Cono, S., Sales, G., Scorrano, L., Giacomello, M., & Montopoli, M. (2022). Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy. Cell Death and Disease, 13(4), Article 398. https://doi.org/10.1038/s41419-022-04741-9

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title = "Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy",

abstract = "Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.",

author = "Caterina Vianello and Veronica Cocetta and Daniela Catanzaro and Dorn, {Gerald W.} and {De Milito}, Angelo and Flavio Rizzolio and Vincenzo Canzonieri and Erika Cecchin and Rossana Roncato and Giuseppe Toffoli and Vincenzo Quagliariello and {Di Mauro}, Annabella and Simona Losito and Nicola Maurea and Scaffa Cono and Gabriele Sales and Luca Scorrano and Marta Giacomello and Monica Montopoli",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = apr,

doi = "10.1038/s41419-022-04741-9",

language = "English",

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Vianello, C, Cocetta, V, Catanzaro, D, Dorn, GW, De Milito, A, Rizzolio, F, Canzonieri, V, Cecchin, E, Roncato, R, Toffoli, G, Quagliariello, V, Di Mauro, A, Losito, S, Maurea, N, Cono, S, Sales, G, Scorrano, L, Giacomello, M & Montopoli, M 2022, 'Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy', Cell Death and Disease, vol. 13, no. 4, 398. https://doi.org/10.1038/s41419-022-04741-9

TY - JOUR

T1 - Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

AU - Vianello, Caterina

AU - Cocetta, Veronica

AU - Catanzaro, Daniela

AU - Dorn, Gerald W.

AU - De Milito, Angelo

AU - Rizzolio, Flavio

AU - Canzonieri, Vincenzo

AU - Cecchin, Erika

AU - Roncato, Rossana

AU - Toffoli, Giuseppe

AU - Quagliariello, Vincenzo

AU - Di Mauro, Annabella

AU - Losito, Simona

AU - Maurea, Nicola

AU - Cono, Scaffa

AU - Sales, Gabriele

AU - Scorrano, Luca

AU - Giacomello, Marta

AU - Montopoli, Monica

PY - 2022/4

Y1 - 2022/4

N2 - Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.

AB - Cisplatin (CDDP) is commonly used to treat a multitude of tumors including sarcomas, ovarian and cervical cancers. Despite recent investigations allowed to improve chemotherapy effectiveness, the molecular mechanisms underlying the development of CDDP resistance remain a major goal in cancer research. Here, we show that mitochondrial morphology and autophagy are altered in different CDDP resistant cancer cell lines. In CDDP resistant osteosarcoma and ovarian carcinoma, mitochondria are fragmented and closely juxtaposed to the endoplasmic reticulum; rates of mitophagy are also increased. Specifically, levels of the mitophagy receptor BNIP3 are higher both in resistant cells and in ovarian cancer patient samples resistant to platinum-based treatments. Genetic BNIP3 silencing or pharmacological inhibition of autophagosome formation re-sensitizes these cells to CDDP. Our study identifies inhibition of BNIP3-driven mitophagy as a potential therapeutic strategy to counteract CDDP resistance in ovarian carcinoma and osteosarcoma.

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VL - 13

JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 4

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ER -

Cisplatin resistance can be curtailed by blunting Bnip3-mediated mitochondrial autophagy

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