Table 1.

The biological factors of radioresistance from the mitochondria perspective.

Factors	Cancer	Ref.	Interaction with Mitochondria	Ref.
Increasing radioresistance
Mutated P53	Various	[57]	−Mutated p53 preserves mtDNA integrity −Mutated p53 improves mt capacity (PGC1α-mediated) −More functional mt scavenge more RT-induced ROS	[55] [56] [10]
TGF-β	HCC	[58]	−TGF-β signaling in CAFs mediates reverse Warburg effect −CAFs’ lactate and pyruvate feed cancer cells’ mt OxPhos −Activated OxPhos helps to restore NADPH −NADPH supports the antioxidant defense system	[59] [60] [61] [62]
IDH1	Glioblastoma	[63]	−Mutated IDH1 enhances mt OxPhos (ROS generation) −Mutated IDH1 downregulates cytochrome c −Cytochrome c can nullify ROS −Thus, IDH1 mutation disrupts the ROS balance	[64] [65] [66]
PARP	Breast Ovarian Prostate Pancreatic HCC	[67] [68]	−PARP requires RAD51 for HR −BRCA2 regulates RAD51 function −BRCA2 requires mt support −Thus, functional mt improves radioresistance by mediating HR	[69] [69] [70]
PI3K/Akt/mTOR pathway	Prostate	[71]	−mTOR upregulates mt proteins responsible for mt metabolism −More functional mt scavenge more RT-induced ROS	[72] [10]
Wnt/β-catenin pathway	Esophageal SCC	[73]	−Wnt upregulates HMGB1 −HMGB1 activates mitochondria −More functional mt scavenge more RT-induced ROS	[73] [74] [10]
NF-κB pathway	Breast Glioma HCC Melanoma NSCLC	[75]	−Enhances mt respiration −Regulates mt dynamics −Regulates mt gene expression	[76]
8-oxo-dG	Esophageal Gastric	[77]	−Serum 8-oxo-DG level represents cellular ROS −Cellular ROS is dependent on mt metabolism	[77] [10]
ATM	Glioma	[78]	−Preserves mtDNA	[79]
XRCC1	NSCLC HNC	[80]	−Preserves mt respiratory chain	[81]
NOTCH2	NSCLC	[82]	−Regulates mitochondrial function	[83]
KEAP1	NSCLC	[82]	−Regulates mitochondrial function −Regulates mitophagy	[84] [85]
FGFR1/3	NSCLC	[82]	−Regulates mitochondrial energy metabolism	[86]
HOTAIR	Breast	[87]	−Regulates mitochondrial function	[88] [89]
AMPK	Glioblastoma	[90]	−Preserves mt biogenesis upon energy stress	[91]
RPA1	Glioblastoma	[92]	−Preserves mtDNA	[93]
RSK2	NSCLC	[94]	−Stimulates mt OxPhos	[95]
LAPTM4B	NPC	[96]	−Activates mTOR −mTOR upregulates mt proteins responsible for mt metabolism −More functional mt scavenge more RT-induced ROS	[97] [72] [10]
Decreasing radioresistance
TNFα	NSCLC	[98]	−Impairs mt complex I and III −Complex III is essential for NADPH activity −Thus, reduces mt capacity to scavenge RT-induced ROS	[99] [100]

Note: This Table is retrieved from the Taghizadeh-Hesary et al. study [32]. Abbreviations: 8-oxo-dG, 8-hydroxy-2′-deoxyguanosine; Akt, protein kinase B; AMPK, serine/threonine kinase AMP-activated protein kinase; ATM, ataxia-telangiectasia mutated; BRCA2, breast cancer gene 2; CAF, cancer-associated fibroblasts; FGFR1/3, fibroblast growth factor 1/3; HCC, hepatocellular carcinoma; HMGB1, high mobility group box 1; HOTAIR, HOX transcript antisense RNA; HR, homologous recombination; IDH1, Isocitrate dehydrogenase 1; KEAP1, Kelch-like ECH-associated protein; LAPTM4B, lysosome-associated transmembrane protein 4B; mt, mitochondrial; mTOR, mammalian target of rapamycin; NADPH, nicotinamide adenine dinucleotide phosphate; NF-κB, nuclear factor κB; NOTCH2, neurogenic locus notch homolog protein 2; NPC, nasopharyngeal carcinoma; NSCLC, non-small cell lung cancer; OxPhos, oxidative phosphorylation; PARP, poly (ADP-ribose) polymerase; PGC-1α, peroxisome proliferator-activated receptor-gamma coactivator 1α; PI3K, phosphoinositide 3-kinases; ROS, reactive oxygen species; RPA1, replication protein A1; RSK2, ribosomal S6 kinase; RT, radiotherapy; SCC, squamous cell carcinoma; TGF-β, transforming growth factor β; TNFα, tumor necrosis factor α; XRCC1, X-ray repair cross complementing 1.