Abstract
Mitochondria are the main fascinating energetic source into the cells. Their number, shape, and dynamism are controlled by the cell’s type and current behavior. The perturbation of the mitochondrial inward system via stress response and/or oncogenic insults could activate several trafficking molecular mechanisms with the intention to solve the problem. In this review, we aimed to clarify the crucial pathways in the mitochondrial system, dissecting the different metabolic defects, with a special emphasis on hematological malignancies. We investigated the pivotal role of mitochondria in the maintenance of hematopoietic stem cells (HSCs) and their main alterations that could induce malignant transformation, culminating in the generation of leukemic stem cells (LSCs). In addition, we presented an overview of LSCs mitochondrial dysregulated mechanisms in terms of (1) increasing in oxidative phosphorylation program (OXPHOS), as a crucial process for survival and self-renewal of LSCs,(2) low levels of reactive oxygen species (ROS), and (3) aberrant expression of B-cell lymphoma 2 (Bcl-2) with sustained mitophagy. Furthermore, these peculiarities may represent attractive new “hot spots” for mitochondrial-targeted therapy. Finally, we remark the potential of the LCS metabolic effectors to be exploited as novel therapeutic targets.
Highlights
Defined in biological vocabulary, mitochondria are “Perpetuum mobile” of the cell and its source of energy
It is a massive protein structure composed of several parts such as voltage-dependent anion channel (VDAC) located on outer mitochondrial membrane (OMM), adenine nucleotide translocase (ANT) located in inner mitochondrial membrane (IMM), and cyclophilin D (CYPD) in the mitochondrial matrix
The preservation of mitochondrial homeostasis is mainly due to the action of the protein permeability transition pore complex (PTPC)
Summary
Mitochondria are “Perpetuum mobile” of the cell and its source of energy. As specified by endosymbiotic theory [1], they originate from prokaryotic cells—alpha-proteobacteria, which during the evolution were imbibed by eukaryotic cells [2] The truth of this theory is sustained by the fact that mitochondria contain their own genetic material, a circular genome that represents mitochondrial DNA (mtDNA), encoding proteins [3,4,5]. Mithochondria have vital roles in numerous cellular processes, including apoptotic activation and cell death, maintenance of ion homeostasis especially calcium, synthesis of phospholipids (for example phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin), of amino acids and heme, among others [16,17]. Mitochondrial stress resulting in altered cellular metabolism and activation of further processes, which lead to the onset of leukemia [25,26,27]
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