Evaluation of Mitochondrial Phagy (Mitophagy) in Human Non-small Adenocarcinoma Tumor Cells

  1. Alizadeh, Javad 1
  2. da Silva Rosa, Simone C. 1
  3. Cordani, Marco 25
  4. Ghavami, Saeid 134
  1. 1 Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
  2. 2 Department of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain
  3. 3 Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada
  4. 4 Faculty of Medicine in Zabrze, University of Technology in Katowice, Zabrze, Poland
  5. 5 Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain
Mostrar afiliaciones +
Libro:
Methods in Molecular Biology

Editorial: John M. Walker

ISSN: 1064-3745,  1940-6029

Año de publicación: 2024

Tipo: Capítulo de Libro

DOI: 10.1007/7651_2024_532 GOOGLE SCHOLAR lock_openAcceso abierto editor

Resumen

Non–small cell lung cancer (NSCLC) is a predominant form of lung cancer characterized by its aggressive nature and high mortality rate, primarily due to late-stage diagnosis and metastatic spread. Recent studies underscore the pivotal role of mitophagy, a selective form of autophagy targeting damaged or superfluous mitochondria, in cancer biology, including NSCLC. Mitophagy regulation may influence cancer cell survival, proliferation, and metastasis by modulating mitochondrial quality and cellular energy homeostasis. Herein, we present a comprehensive methodology developed in our laboratory for the evaluation of mitophagy in NSCLC tumor cells. Utilizing a combination of immunoblotting, immunocytochemistry, and fluorescent microscopy, we detail the steps to quantify early and late mitophagy markers and mitochondrial dynamics. Our findings highlight the potential of targeting mitophagy pathways as a novel therapeutic strategy in NSCLC, offering insights into the complex interplay between mitochondrial dysfunction and tumor progression. This study not only sheds light on the significance of mitophagy in NSCLC but also establishes a foundational approach for its investigation, paving way for future research in this critical area of cancer biology.

Referencias bibliográficas

  • Brenner DR, Poirier A, Woods RR, Ellison LF, Billette JM, Demers AA et al (2022) Projected estimates of cancer in Canada in 2022. CMAJ 194(17):E601–E6E7
  • Alizadeh J, Kavoosi M, Singh N, Lorzadeh S, Ravandi A, Kidane B et al (2023) Regulation of autophagy via carbohydrate and lipid metabolism in cancer. Cancers (Basel) 15(8):2195
  • Expert Consensus P, Kidane B, Bott M, Spicer J, Backhus L, Chaft J et al (2023) The American Association for Thoracic Surgery (AATS) 2023 Expert Consensus Document: staging and multidisciplinary management of patients with early-stage non-small cell lung cancer. J Thorac Cardiovasc Surg 166(3):637–654
  • Alizadeh J, Shojaei S, Sepanjnia A, Hashemi M, Eftekharpour E, Ghavami S (2019) Simultaneous detection of autophagy and epithelial to mesenchymal transition in the non-small cell lung cancer cells. Methods Mol Biol 1854:87–103
  • Araghi M, Mannani R, Heidarnejad Maleki A, Hamidi A, Rostami S, Safa SH et al (2023) Recent advances in non-small cell lung cancer targeted therapy; an update review. Cancer Cell Int 23(1):162
  • Nikseresht M, Shahverdi M, Dehghani M, Abidi H, Mahmoudi R, Ghalamfarsa G et al (2019) Association of single nucleotide autophagy-related protein 5 gene polymorphism rs2245214 with susceptibility to non-small cell lung cancer. J Cell Biochem 120(2):1924–1931
  • Debnath J, Gammoh N, Ryan KM (2023) Autophagy and autophagy-related pathways in cancer. Nat Rev Mol Cell Biol 24(8):560–575
  • Cordani M, Strippoli R, Trionfetti F, Barzegar Behrooz A, Rumio C, Velasco G et al (2024) Immune checkpoints between epithelial-mesenchymal transition and autophagy: a conflicting triangle. Cancer Lett 585:216661
  • Behrooz AB, Cordani M, Fiore A, Donadelli M, Gordon JW, Klionsky DJ, Ghavami S (2024) The obesity-autophagy-cancer axis: mechanistic insights and therapeutic perspectives. Semin Cancer Biol 99:24–44
  • Vargas JNS, Hamasaki M, Kawabata T, Youle RJ, Yoshimori T (2023) The mechanisms and roles of selective autophagy in mammals. Nat Rev Mol Cell Biol 24(3):167–185
  • Behrooz AB, Cordani M, Donadelli M, Ghavami S (2024) Metastatic outgrowth via the two-way interplay of autophagy and metabolism. Biochim Biophys Acta Mol basis Dis 1870(3):166824
  • Kirkin V, Rogov VV (2019) A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. Mol Cell 76(2):268–285
  • Pickles S, Vigie P, Youle RJ (2018) Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol 28(4):R170–R185
  • Alizadeh J, da Silva Rosa SC, Weng X, Jacobs J, Lorzadeh S, Ravandi A et al (2023) Ceramides and ceramide synthases in cancer: focus on apoptosis and autophagy. Eur J Cell Biol 102(3):151337
  • Huang CF, Hsieh YH, Yang SF, Kuo CH, Wang PH, Liu CJ, Lin RC (2023) Mitophagy effects of Protodioscin on human osteosarcoma cells by inhibition of p38MAPK targeting NIX/LC3 Axis. Cells 12(3):395
  • Qin S, Liu C, Chen Y, Yao M, Liao S, Xin W et al (2023) Cobaltosic oxide-polyethylene glycol-triphenylphosphine nanoparticles ameliorate the acute-to-chronic kidney disease transition by inducing BNIP3-mediated mitophagy. Kidney Int 103(5):903–916
  • Bi Y, Liu S, Qin X, Abudureyimu M, Wang L, Zou R et al (2024) FUNDC1 interacts with GPx4 to govern hepatic ferroptosis and fibrotic injury through a mitophagy-dependent manner. J Adv Res 55:45–60
  • Fang Q, Zheng S, Chen Q, Chen L, Yang Y, Wang Y et al (2023) The protective effect of inhibiting mitochondrial fission on the juvenile rat brain following PTZ kindling through inhibiting the BCL2L13/LC3 mitophagy pathway. Metab Brain Dis 38(2):453–466
  • Yamada T, Murata D, Adachi Y, Itoh K, Kameoka S, Igarashi A et al (2018) Mitochondrial stasis reveals p62-mediated ubiquitination in Parkin-independent Mitophagy and mitigates nonalcoholic fatty liver disease. Cell Metab 28(4):588–604 e5
  • Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O’Reilly N et al (2019) Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins. Nat Commun 10(1):2055
  • Villa E, Marchetti S, Ricci JE (2018) No Parkin zone: Mitophagy without Parkin. Trends Cell Biol 28(11):882–895
  • Johansen T, Lamark T (2020) Selective autophagy: ATG8 family proteins, LIR motifs and cargo receptors. J Mol Biol 432(1):80–103
  • Su J, Liu D, Yang F, Zuo MQ, Li C, Dong MQ et al (2022) Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors. Proc Natl Acad Sci USA 119(26):e2200158119
  • Chan NC, Salazar AM, Pham AH, Sweredoski MJ, Kolawa NJ, Graham RL et al (2011) Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy. Hum Mol Genet 20(9):1726–1737
  • Franco-Iborra S, Cuadros T, Parent A, Romero-Gimenez J, Vila M, Perier C (2018) Defective mitochondrial protein import contributes to complex I-induced mitochondrial dysfunction and neurodegeneration in Parkinson’s disease. Cell Death Dis 9(11):1122
  • Luciani A, Schumann A, Berquez M, Chen Z, Nieri D, Failli M et al (2020) Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency. Nat Commun 11(1):970
  • Zhang C, Zeng C, Xiong S, Zhao Z, Wu G (2022) A mitophagy-related gene signature associated with prognosis and immune microenvironment in colorectal cancer. Sci Rep 12(1):18688
  • Li Q, Chu Y, Li S, Yu L, Deng H, Liao C et al (2022) The oncoprotein MUC1 facilitates breast cancer progression by promoting Pink1-dependent mitophagy via ATAD3A destabilization. Cell Death Dis 13(10):899
  • Yu H, Liu Q, Jin M, Huang G, Cai Q (2023) Comprehensive analysis of mitophagy-related genes in NSCLC diagnosis and immune scenery: based on bulk and single-cell RNA sequencing data. Front Immunol 14:1276074
  • Liu Z, Shan S, Yuan Z, Wu F, Zheng M, Wang Y et al (2023) Mitophagy bridges DNA sensing with metabolic adaption to expand lung cancer stem-like cells. EMBO Rep 24(2):e54006
  • Qin C, Wang Y, Zhao B, Li Z, Li T, Yang X et al (2023) STOML2 restricts mitophagy and increases chemosensitivity in pancreatic cancer through stabilizing PARL-induced PINK1 degradation. Cell Death Dis 14(3):191
  • Hawk MA, Schafer ZT (2018) RIPK1-dependent mitophagy: a novel mechanism to eliminate cells detached from the extracellular matrix. Mol Cell Oncol 5(4):e1465015
  • Greier MC, Runge A, Dudas J, Pider V, Skvortsova II, Savic D, Riechelmann H (2022) Mitochondrial dysfunction and epithelial to mesenchymal transition in head neck cancer cell lines. Sci Rep 12(1):13255
  • Alizadeh J, Glogowska A, Thliveris J, Kalantari F, Shojaei S, Hombach-Klonisch S et al (2018) Autophagy modulates transforming growth factor beta 1 induced epithelial to mesenchymal transition in non-small cell lung cancer cells. Biochim Biophys Acta, Mol Cell Res 1865(5):749–768
  • Abdelmaksoud NM, Abulsoud AI, Abdelghany TM, Elshaer SS, Rizk SM, Senousy MA (2023) Mitochondrial remodeling in colorectal cancer initiation, progression, metastasis, and therapy: a review. Pathol Res Pract 246:154509