scholarly journals The Contextual Essentiality of Mitochondrial Genes in Cancer

Author(s):  
Luke W. Thomas ◽  
Margaret Ashcroft

Mitochondria are key organelles in eukaryotic evolution that perform crucial roles as metabolic and cellular signaling hubs. Mitochondrial function and dysfunction are associated with a range of diseases, including cancer. Mitochondria support cancer cell proliferation through biosynthetic reactions and their role in signaling, and can also promote tumorigenesis via processes such as the production of reactive oxygen species (ROS). The advent of (nuclear) genome-wide CRISPR-Cas9 deletion screens has provided gene-level resolution of the requirement of nuclear-encoded mitochondrial genes (NEMGs) for cancer cell viability (essentiality). More recently, it has become apparent that the essentiality of NEMGs is highly dependent on the cancer cell context. In particular, key tumor microenvironmental factors such as hypoxia, and changes in nutrient (e.g., glucose) availability, significantly influence the essentiality of NEMGs. In this mini-review we will discuss recent advances in our understanding of the contribution of NEMGs to cancer from CRISPR-Cas9 deletion screens, and discuss emerging concepts surrounding the context-dependent nature of mitochondrial gene essentiality.

HortScience ◽  
2006 ◽  
Vol 41 (4) ◽  
pp. 1082B-1082
Author(s):  
Shiow Wang ◽  
Kimberly Lewers ◽  
Linda Bowman ◽  
Min Ding

Representatives of three species of strawberries (Fragaria virginiana, F. chiloensis and F. ×ananassa) were evaluated for antioxidant capacity, scavenging capacity for reactive oxygen species (ROO·, ·OH, 1O2 and O2 .-), and inhibitory effect on proliferation of A549 human lung epithelial cancer cells. Differences among the strawberry genotypes were observed for all three qualities. High antioxidant and scavenging capacities were found in `CFRA 0982', `JP 95-1-1', NC 95-19-1 and RH 30. Lowest antioxidant and scavenging capacities were found in `Allstar'. There was also a relationship between scavenging capacity and the inhibition of cancer cell proliferation. The correlations (R2) between the scavenging capacities for the reactive oxygen species and the inhibition of cancer cell proliferation were 0.8074, 0.8279, 0.7862 and 0.7761 for ROO·, ·OH, 1O2 and O2.-, respectively. These results suggest that antioxidants, specifically their scavenging capacities, may play an important role in the antiproliferative activity of strawberries. This study also identified strawberry germplasm of value in developing cultivars useful for cancer prevention.


2014 ◽  
Vol 20 (4) ◽  
pp. 650-661 ◽  
Author(s):  
Nishi Srivastava ◽  
Rahul K. Kollipara ◽  
Dinesh K. Singh ◽  
Jessica Sudderth ◽  
Zeping Hu ◽  
...  

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sheng-Long Kan ◽  
Ting-Ting Shen ◽  
Jin-Hua Ran ◽  
Xiao-Quan Wang

Abstract Background Mitochondrial gene transfer/loss is common in land plants, and therefore the fate of missing mitochondrial genes has attracted more and more attention. The gene content of gymnosperm mitochondria varies greatly, supplying a system for studying the evolutionary fate of missing mitochondrial genes. Results Here, we studied the tempo and pattern of mitochondrial gene transfer/loss in gymnosperms represented by all 13 families, using high-throughput sequencing of both DNA and cDNA. All 41 mitochondrial protein-coding genes were found in cycads, Ginkgo and Pinaceae, whereas multiple mitochondrial genes were absent in Conifer II and Gnetales. In Conifer II, gene transfer from mitochondria to the nucleus followed by loss of the mitochondrial copy was common, but complete loss of a gene in both mitochondrial and nuclear genomes was rare. In contrast, both gene transfer and loss were commonly found in Gnetales. Notably, in Conifer II and Gnetales, the same five mitochondrial genes were transferred to the nuclear genome, and these gene transfer events occurred, respectively, in ancestors of the two lineages. A two-step transfer mechanism (retroprocessing and subsequent DNA-mediated gene transfer) may be responsible for mitochondrial gene transfer in Conifer II and Gnetales. Moreover, the mitochondrial gene content variation is correlated with gene length, GC content, hydrophobicity, and nucleotide substitution rates in land plants. Conclusions This study reveals a complete evolutionary scenario for variations of mitochondrial gene transferring in gymnosperms, and the factors responsible for mitochondrial gene content variation in land plants.


2021 ◽  
Author(s):  
Chelsea U. Kidwell ◽  
Joseph R. Casalini ◽  
Soorya Pradeep ◽  
Sandra D. Scherer ◽  
Daniel Greiner ◽  
...  

Lateral transfer of mitochondria occurs in many physiological and pathological conditions. Given that mitochondria provide essential energy for cellular activities, mitochondrial transfer is currently thought to promote the rescue of damaged cells. We report that mitochondrial transfer occurs between macrophages and breast cancer cells, leading to increased cancer cell proliferation. Unexpectedly, transferred macrophage mitochondria are dysfunctional, lacking mitochondrial membrane potential. Rather than performing essential mitochondrial activities, transferred mitochondria accumulate reactive oxygen species which activates ERK signaling, indicating that transferred mitochondria act as a signaling source that promotes cancer cell proliferation. We also demonstrate that pro-tumorigenic M2-like macrophages exhibit increased mitochondrial transfer to cancer cells. Collectively, our findings reveal how mitochondrial transfer is regulated and leads to sustained functional changes in recipient cells.


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