Defining the momiome: Promiscuous information transfer by mobile mitochondria and the mitochondrial genome

Abstract

Mitochondria are complex intracellular organelles that have long been identified as the powerhouses of eukaryotic cells because of the central role they play in oxidative metabolism. A resurgence of interest in the study of mitochondria during the past decade has revealed that mitochondria also play key roles in cell signaling, proliferation, cell metabolism and cell death, and that genetic and/or metabolic alterations in mitochondria contribute to a number of diseases, including cancer. Mitochondria have been identified as signaling organelles, capable of mediating bidirectional intracellular information transfer: anterograde (from nucleus to mitochondria) and retrograde (from mitochondria to nucleus). More recently, evidence is now building that the role of mitochondria extends to intercellular communication as well, and that the mitochondrial genome (mtDNA) and even whole mitochondria are indeed mobile and can mediate information transfer between cells. We define this promiscuous information transfer function of mitochondria and mtDNA as “momiome” to include all mobile functions of mitochondria and the mitochondrial genome. Herein we review the “momiome” and explore its role in cancer development, progression, and treatment.

Mitochondria in the Nuclei of Rat Myocardial Cells

“…In eukaryotic cells, mitochondria take part in intracellular regulations mediated by cross-talk between mitochondria and the nucleus. This interaction is represented by anterograde (nucleus-mitochondrion) and retrograde (mitochondrion-nucleus) signaling [32]. This cross-talk includes exchange by ATP/ADP, regulatory proteins and genetic material going in both directions.…”

“…This cross-talk includes exchange by ATP/ADP, regulatory proteins and genetic material going in both directions. Bidirectional transport of genetic material is of primary interest for molecular biologists due to its high relevance to the evolution of eukaryotic genomes [27][28][29] and the occurrence of diseases through regulation of gene expression, possibly by non-coding RNAs originating both from mitochondria [32] and nuclei [31][32][33][34][54][55][56][57]. The so-called "escape" of nucleic acids from nuclei and mitochondria [58] seems to be part of a well-designed strategy of communication of genomes rather than being an occasional stochastic process.…”

“…A common opinion is that the transfer of mitochondrial DNA to the nucleus has contributed to the evolution of eukaryotic genomes [27][28][29]. Mitochondrial DNA transfer to the nucleus is an established fact, possibly playing both normal [30] and pathological [31,32] roles. Vice versa, anterograde signaling (from nucleus to mitochondria) includes numerous regulatory factors coordinating the function of subcellular organelles and integrating cellular and environmental signals, such as nuclear respiratory factor 1 (NRF1) [33], nuclear factor erythroid 2-like 2 [34] (NFE2L2 or NRF2), peroxisome proliferator-activated receptors (PPARs), and estrogen-related receptors (ERRs) [35], as well as many others that regulate mitochondrial-specific activities.…”

Mitocans Revisited: Mitochondrial Targeting as Efficient Anti-Cancer Therapy

“…They have multiple important functions, including controlling adenosine triphosphate (ATP) generation, metabolic signalling, proliferation, redox homeostasis, and promotion/suppression of apoptotic signalling pathways. Genetic and/or metabolic alterations in mitochondria contribute to many human diseases, including cancer [1]. Although glycolysis was traditionally considered as the major source of energy in cancer cells, consistent with the so-called "Warburg effect" first suggested almost a century ago, referring to the elevated uptake of glucose that characterizes the majority of cancers, the mitochondrial function known as oxidative phosphorylation (OXPHOS) has been recently recognized to play a key role in oncogenesis [2,3].…”

Healthy Mitochondria: The Brake of Cell Proliferation of Malignant Melanoma

“…[1 , 2 Thus, introducing healthy mitochondria into tumor cells is proposed to have a high efficacy in preventing tumor growth. [3,4 Currently,exogenous healthy mitochondria have been utilized in treating several carcinoma, including breast cancer, pancreatic cancer, and glioma, and similar results exhibited the excellent antitumor activity of the healthy mitochondria. [5 , 6 , 7 In our recent studies, we have examined the anti-tumor potential of mitochondria derived from young and aged mouse liver, and found that mitochondria from young mice have stronger anti-melanoma effects in comparison with that of the aged mice.…”