Mitochondrial transfer between cells can rescue aerobic respiration

Abstract

Current theory indicates that mitochondria were obtained 1.5 billion years ago from an ancient prokaryote. The mitochondria provided the capacity for aerobic respiration, the creation of the eukaryotic cell, and eventually complex multicellular organisms. Recent reports have found that mitochondria play essential roles in aging and determining lifespan. A variety of heritable and acquired diseases are linked to mitochondrial dysfunction. We report here that mitochondria are more dynamic than previously considered: mitochondria or mtDNA can move between cells. The active transfer from adult stem cells and somatic cells can rescue aerobic respiration in mammalian cells with nonfunctional mitochondria.human bone marrow ͉ nonhematopoietic ͉ stem͞progenitor cells ͉ ischemia M itochondria are essential organelles in plant and animal cells that are from a prokaryotic ancestor and play a key role in processes such as oxidative phosphorylation, aerobic metabolism of glucose and fat, calcium signaling, and apoptosis (1, 2). The human mitochondrial genome is 16,568 bp and encodes a limited number of mitochondria-specific proteins, rRNAs, and tRNAs (3). All other mitochondrial proteins are encoded in the nucleus. The mitochondrial genome is maternally inherited and undergoes a high rate of mutation because mtDNA is not protected by histones, is inefficiently repaired (4), and is exposed to oxygen radicals generated by oxidative phosphorylation (1).Nearly every tissue contains stem-like progenitor cells that repair tissues after damage (5), but local repair can be supplemented by stem-like progenitor cells from the bone marrow. Stem͞progenitor cells repair tissues by differentiating to replace lost cells, providing cytokines and growth factors, and by cell fusion with endogenous cells.In this article, we ask whether stem͞progenitor cells or other somatic cells can repair cells with nonfunctional mitochondria by transfer of functional mitochondria or mtDNA. We used cells that were pretreated with ethidium bromide so that the mtDNA became mutated and depleted and the cells became incapable of aerobic respiration and growth (A549 °cells), except in a permissive medium containing uridine and pyruvate to supplement anaerobic glycolysis (6, 7). The A549 °cells were cocultured with either adult nonhematopoietic stem͞progenitor cells from human bone marrow (hMSCs) or with skin fibroblasts. The cocultures produced clones of rescued A549 °cells with functional mitochondria. ResultsRescue of A549 °Cells by Coculture with hMSCs. PCR assays indicated that a number of mitochondrial genes and DNA sequences were absent or depleted in A549 °cells: the genes for cytochrome oxidase I and II, the gene for tRNA leucine, and hypervariable regions I and II of the D loop (Fig. 1A). Some of the PCR products may have been generated by nonfunctional nuclear pseudogenes in the A549 °cells that are only detectable after mtDNA depletion (8). Sequencing of the PCR products demonstrated additional extensive damage and mutations of A549 °mtDNA (data not sho...

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

“…In addition, it has been shown that the mitochondria can access thick nanotubes. Rescue of aerobic respiration in cells deficient in mitochondria was demonstrated by the intercellular transfer of whole mitochondria or mitochondrial DNA from normal cells, possibly involving membrane nanotubes formation (80). At present, the best datum for functional relevance of membrane nanotubules in immune-cell biology is the demonstration that they mediate communication of antigenic signals between myeloid cells (9,77).…”

Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration

“…In a report by Spees et al, active mitochondrial transfer occurred between adult stem cells and somatic cells, resulting in rescue of aerobic respiration in mammalian cells 11. Astrocytes were reported to shed mitochondria via membrane vesicles,7 which were then effectively transferred into neurons in response to cerebral ischemia, enhancing cell survival signaling 8.…”

Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/ scid mice

“…MSCs are readily obtained from a patient and rapidly expanded in culture so that it is feasible to administer very large numbers of autologous cells. After systemic infusion, the cells home to injured tissues and repair them by several different mechanisms, including differentiating into multiple cellular phenotypes, providing cytokines and chemokines (17), enhancing the proliferation of tissue-endogenous stem͞progenitor cells (18), and perhaps cell fusion (19) or transfer of mitochondria (20). In addition, MSCs suppress some immune reactions (21).…”