Mitophagy and Cancer Formation
The role of mitochondria, the double-membrane organelles supplying energy to cells, in the development of cancer (carcinogenesis) and cancer progression is a hot bed for research.Mitochondria are the basic units where energy is produced and the cell gets its respiration.
Mitochondria can be damged due to various stresses in the cell .The damaged or altered mitochondria need to be identified and removed for proper functioning of the cell,otherwise the damaged cells can alter a cells function.It is well known that in cancer cells, mitochondrial pathways are altered to meet the increased energy needs of the cancer cells and to handle oxidative stress. Mitochondrial dysfunction is understood to arise from a dysregulation of mitophagy.
Mitophagy is a physiological mechanism of quality control by which damaged mitochondria are destroyed by the body’s regulatory mechanism.The aim of researchers has been to find whether mitophagy acts to promote or to limit cancer formation and explore opportunity for anti-cancer drug targets.
Mitophagy has been recently implicated in reshaping the metabolic pathways within cancer cells to enable the adaptive and survival ability of cancer cells. The connection between cancer formation and mitophagy is complex.
Mitochondria are the primary site for energy ( ATP) production, but they are also the place where reactive oxygen species (ROS) production and glucose digestion(metabolism) occur. Generally, cancer cells undergo a reprogramming to gain advantages with respect to normal cells.
Mitophagy, by eliminating aged dysfunctional mitochondria helps in maintaining mitochondrial and cellular integrity in all the cells including red blood cells, muscles, connective tissues etc. Thus, a defect in mitophagy can lead to loss of tissue regulation and development of cancers.
Genetic defects are known to be a common factor in a wide range of cancers. Modifications and mutations in genes involved in mitophagy are frequently observed in several tumors, and this raises the possibility that all these alterations provide a basis for cancer formation.
Deletion of Parkin protein expression has been described in colorectal cancer. A similar cancer suppressive role of Parkin is also detected in breast cancer where a non-function of mitophagy influences cancer progression. The understanding of the alterationsin signal exchange has been seen in several cancers such as ovarian cancer, glioblastoma, and neuroblastoma. These pathways have been implicated in initiation and progression of liver cancer also.
It is challenging to predict the role that mitophagy has on cancer cells because it depends on different factors like cancer type, cancer stage, genetic background, and the fine balance between cellular demand and availability. Thus, mitophagic alterations can have a dual role acting as cancer suppressors like during Atg5 or Atg7 depletion, considered essential molecules for the induction of autophagy, or promoters like in FUNDC1, and PINK1 deficiency.