Mitochondrial function and dysfunction in cancer and their potential as anti-cancer targets

Dear Colleagues,

The mitochondrion, a discrete sub-cellular organelle comprising some 1000 different proteins, mediates basic life functions and contains key components of biosynthetic pathways, as well as serving as the site where cellular decisions leading to apoptosis (programmed cell death) are taken. Mitochondria perform a variety of crucial cell functions, including energy production, Ca2+ signaling and maintenance of Ca2+ homeostasis, metabolism of amino acids, lipids, and iron, modulation of the cell’s redox potential, osmotic regulation and pH control, as well as being the  site of reactive oxygen species (ROS) generation and an essential component of the apoptotic machinery. Changes in these parameters can impact biosynthetic pathways, cellular signal transduction pathways, and epigenetics, shifting the cell from the quiescent, differentiated state to one of actively proliferation, as occurs in cancer. Indeed, the signaling pathways that govern mitochondrial function, mitochondrial integrity, cell viability and apoptosis have been addressed in many studies, with mitochondrial targeting strategies having recently gained momentum.

The association of mitochondria with cancer was first presented over 70 years ago by Otto Heinrich Warburg and his colleagues, who hypothesized that dysfunctional mitochondria may be the cause of higher rates of aerobic glycolysis (termed the 'Warburg effect”), with this gradual and cumulative decrease in mitochondrial activity being associated with malignant transformation. However, many studies conducted since have demonstrated that functional mitochondria are essential for the cancer cell and have identified pleiotropic roles of mitochondria in tumorigenesis.

Given their roles in bioenergetics, in biosynthetic pathways and as signaling organelles sensing stress, mitochondria are central to cellular adaptation to the environment. As such, it is not surprising that mitochondria are important mediators of tumorigenesis, a process requiring flexibility in adapting to cellular and environmental alterations. Indeed, differences in mitochondrial structure and function between normal and cancer cells have been reported. These changes can provide the biological basis for preferential targeting of cancer cells. Thus, uncovering the mechanisms responsible for altered mitochondrial function during tumorigenesis is critical for developing the next generation of cancer therapeutics. Indeed, appreciation that mitochondria play central roles in cellular energy generation, metabolism, apoptosis and necrosis carry far-reaching implications and provide solid rationale and a strong biological basis for developing mitochondria-targeted anti-cancer agents.

Scientists studying mitochondria- and cancer-associated topics, including but not limited to oxidative stress, organelle biogenesis, apoptosis, necrosis, import and folding of mitochondrial proteins, membrane synthesis, structure and dynamics, Ca2+ homeostasis, the mitochondrial genetic system, mitochondria-interacting proteins, such as hexokinase, anti- and pro-apoptotic proteins, p53, as well as ER-mitochondria interactions and cancer, are invited to contribute to this special issue.

Prof. Varda Shoshan-Barmatz
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.