mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt)
نویسندگان
چکیده
While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPRmt) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPRmt has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPRmt may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPRmt do not. This review aims at offering an overview of the confusing literature on mtDNA mutations and metastasis and the more recent work on the UPRmt in this setting.
منابع مشابه
Potential involvement of the mitochondrial unfolded protein response in depressive-like symptoms in mice.
Many evidences strongly suggest that a mitochondrial deficit is implicated in major depression. A mitochondrial deficit leads to mitochondrial stress responses, including the mitochondrial unfolded protein response (UPRmt), which is associated with certain brain disorders such as spastic paraplegia and Parkinson's disease. However, there is no evidence regarding the relationship between depress...
متن کاملThe Mitochondrial Unfolded Protein Response as a Non-Oncogene Addiction to Support Adaptation to Stress during Transformation in Cancer and Beyond
Upon accumulation of misfolded proteins in the mitochondria, the mitochondrial unfolded protein response (UPRmt) is activated. This review focuses on the role of this response in cancer. We discuss evidence that during transformation, the UPRmt may play an essential role in the maintenance of the integrity of the mitochondria in the face of increased oxidative stress. However, the role of the U...
متن کاملFragile lifespan expansion by dietary mitohormesis in C. elegans
Mitochondrial function is central to longevity and an imbalance in mitonuclear protein homeostasis activates a protective response called the mitochondrial unfolded protein response (UPRmt). Toxic compounds damaging mitochondria trigger the UPRmt, but at sublethal doses these insults extend lifespan in simple animals like C. elegans. Mitochondria are the main energy suppliers in eukaryotes, but...
متن کاملThe Mitochondrial Unfolded Protein Response Protects against Anoxia in Caenorhabditis elegans
The mitochondrial unfolded protein response (UPRmt) is a surveillance pathway that defends proteostasis in the "powerhouse" of the cell. Activation of the UPRmt protects against stresses imposed by reactive oxygen species, respiratory chain deficits, and pathologic bacteria. Consistent with the UPRmt's role in adaption, we found that either its pharmacological or genetic activation by ethidium ...
متن کاملPGAM5 promotes lasting FoxO activation after developmental mitochondrial stress and extends lifespan in Drosophila
The mitochondrial unfolded protein response (UPRmt) has been associated with long lifespan across metazoans. In Caenorhabditis elegans, mild developmental mitochondrial stress activates UPRmt reporters and extends lifespan. We show that similar developmental stress is necessary and sufficient to extend Drosophila lifespan, and identify Phosphoglycerate Mutase 5 (PGAM5) as a mediator of this res...
متن کامل