bims-mitrat Biomed News
on Mitochondrial transplantation and transfer
Issue of 2024–05–05
nine papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute
  1. Mitochondrial transfer mediates endothelial cell engraftment through mitophagy.
  2. Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart.
  3. Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches.
  4. Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions.
  5. Mitochondrial administration alleviates lead- and cadmium-induced toxicity in rat renal cells.
  6. Mitochondrial genome transfer drives metabolic reprogramming in adjacent colonic epithelial cells promoting TGFβ1-mediated tumor progression.
  7. Mitochondrial redox state, bioenergetics, and calcium transport in caloric restriction: A metabolic nexus.
  8. Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics.
  9. The absence of the ribosomal protein Rpl2702 elicits the MAPK-mTOR signaling to modulate mitochondrial morphology and functions.
  1. Nature. 2024 May 01.
    Mitochondrial transfer mediates endothelial cell engraftment through mitophagy.
    Ruei-Zeng Lin, Gwang-Bum Im, Allen Chilun Luo, Yonglin Zhu, Xuechong Hong, Joseph Neumeyer, Hong-Wen Tang, Norbert Perrimon, Juan M Melero-Martin.
      Ischaemic diseases such as critical limb ischaemia and myocardial infarction affect millions of people worldwide1. Transplanting endothelial cells (ECs) is a promising therapy in vascular medicine, but engrafting ECs typically necessitates co-transplanting perivascular supporting cells such as mesenchymal stromal cells (MSCs), which makes clinical implementation complicated2,3. The mechanisms that enable MSCs to facilitate EC engraftment remain elusive. Here we show that, under cellular stress, MSCs transfer mitochondria to ECs through tunnelling nanotubes, and that blocking this transfer impairs EC engraftment. We devised a strategy to artificially transplant mitochondria, transiently enhancing EC bioenergetics and enabling them to form functional vessels in ischaemic tissues without the support of MSCs. Notably, exogenous mitochondria did not integrate into the endogenous EC mitochondrial pool, but triggered mitophagy after internalization. Transplanted mitochondria co-localized with autophagosomes, and ablation of the PINK1-Parkin pathway negated the enhanced engraftment ability of ECs. Our findings reveal a mechanism that underlies the effects of mitochondrial transfer between mesenchymal and endothelial cells, and offer potential for a new approach for vascular cell therapy.
    DOI:  https://doi.org/10.1038/s41586-024-07340-0
  2. Korean J Physiol Pharmacol. 2024 05 01. 28(3): 209-217
    Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart.
    Jehee Jang, Ki-Woon Kang, Young-Won Kim, Seohyun Jeong, Jaeyoon Park, Jihoon Park, Jisung Moon, Junghyun Jang, Seohyeon Kim, Sunghun Kim, Sungjoo Cho, Yurim Lee, Hyoung Kyu Kim, Jin Han, Eun-A Ko, Sung-Cherl Jung, Jung-Ha Kim, Jae-Hong Ko.
      In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.
    Keywords:  Autografts; Mitochondria; Myocardial ischemia; Myocardial reperfusion; Oxygen consumption; Transplantation
    DOI:  https://doi.org/10.4196/kjpp.2024.28.3.209
  3. Neurol Sci. 2024 Apr 27.
    Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches.
    Gokhan Burcin Kubat, Pasquale Picone.
      Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.
    Keywords:  Amyotrophic lateral sclerosis; Mitochondria; Mitochondrial transplantation; Skeletal muscle dysfunction
    DOI:  https://doi.org/10.1007/s10072-024-07508-6
  4. Front Endocrinol (Lausanne). 2024 ;15 1361289
    Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions.
    Wenhan Ju, Yuewen Zhao, Yi Yu, Shuai Zhao, Shan Xiang, Fang Lian.
      Mitochondria plays an essential role in regulating cellular metabolic homeostasis, proliferation/differentiation, and cell death. Mitochondrial dysfunction is implicated in many age-related pathologies. Evidence supports that the dysfunction of mitochondria and the decline of mitochondrial DNA copy number negatively affect ovarian aging. However, the mechanism of ovarian aging is still unclear. Treatment methods, including antioxidant applications, mitochondrial transplantation, emerging biomaterials, and advanced technologies, are being used to improve mitochondrial function and restore oocyte quality. This article reviews key evidence and research updates on mitochondrial damage in the pathogenesis of ovarian aging, emphasizing that mitochondrial damage may accelerate and lead to cellular senescence and ovarian aging, as well as exploring potential methods for using mitochondrial mechanisms to slow down aging and improve oocyte quality.
    Keywords:  aging; fertility preservation; mechanism; mitochondria; oocyte
    DOI:  https://doi.org/10.3389/fendo.2024.1361289
  5. Cell Biol Int. 2024 Apr 29.
    Mitochondrial administration alleviates lead- and cadmium-induced toxicity in rat renal cells.
    Enayatollah Seydi, Alireza Kanani Nambani, Ali Khorasani, Farzaneh Kamranfar, Abdollah Arjmand, Jalal Pourahmad.
      The role of heavy metals such as lead (Pb) and cadmium (Cd) in the etiology of many diseases has been proven. Also, these heavy metals can affect the normal mitochondrial function. Mitochondrial administration therapy is one of the methods used by researchers to help improve mitochondrial defects and diseases. The use of isolated mitochondria as a therapeutic approach has been investigated in in vivo and in vitro studies. Accordingly, in this study, the effects of mitochondrial administration on the improvement of toxicity caused by Pb and Cd in renal proximal tubular cells (RPTC) have been investigated. The results showed that treatment to Pb and Cd caused an increase in the level of free radicals, lipid peroxidation (LPO) content, mitochondrial and lysosomal membrane damage, and also a decrease in the reduced glutathione content in RPTC. In addition, reports have shown an increase in oxidized glutathione content and changes in energy (ATP) levels. Following, the results have shown the protective role of mitochondrial administration in improving the toxicity caused by Pb and Cd in RPTC. Furthermore, the mitochondrial internalization into RPT cells is mediated through actin-dependent endocytosis. So, it could be suggested that the treatment of Pb- and Cd-induced cytotoxicity in RPTC could be carried out through mitochondria administration.
    Keywords:  cadmium; lead; mitochondria transplantation; oxidative stress; renal proximal tubular (RPT) cells
    DOI:  https://doi.org/10.1002/cbin.12165
  6. Nat Commun. 2024 Apr 30. 15(1): 3653
    Mitochondrial genome transfer drives metabolic reprogramming in adjacent colonic epithelial cells promoting TGFβ1-mediated tumor progression.
    Bingjie Guan, Youdong Liu, Bowen Xie, Senlin Zhao, Abudushalamu Yalikun, Weiwei Chen, Menghua Zhou, Qi Gu, Dongwang Yan.
      Although nontumor components play an essential role in colon cancer (CC) progression, the intercellular communication between CC cells and adjacent colonic epithelial cells (CECs) remains poorly understood. Here, we show that intact mitochondrial genome (mitochondrial DNA, mtDNA) is enriched in serum extracellular vesicles (EVs) from CC patients and positively correlated with tumor stage. Intriguingly, circular mtDNA transferred via tumor cell-derived EVs (EV-mtDNA) enhances mitochondrial respiration and reactive oxygen species (ROS) production in CECs. Moreover, the EV-mtDNA increases TGFβ1 expression in CECs, which in turn promotes tumor progression. Mechanistically, the intercellular mtDNA transfer activates the mitochondrial respiratory chain to induce the ROS-driven RelA nuclear translocation in CECs, thereby transcriptionally regulating TGFβ1 expression and promoting tumor progression via the TGFβ/Smad pathway. Hence, this study highlights EV-mtDNA as a major driver of paracrine metabolic crosstalk between CC cells and adjacent CECs, possibly identifying it as a potential biomarker and therapeutic target for CC.
    DOI:  https://doi.org/10.1038/s41467-024-48100-y
  7. Free Radic Biol Med. 2024 Apr 25. pii: S0891-5849(24)00421-0. [Epub ahead of print]219 195-214
    Mitochondrial redox state, bioenergetics, and calcium transport in caloric restriction: A metabolic nexus.
    Eloisa A Vilas-Boas, Alicia J Kowaltowski.
      Mitochondria congregate central reactions in energy metabolism, many of which involve electron transfer. As such, they are expected to both respond to changes in nutrient supply and demand and also provide signals that integrate energy metabolism intracellularly. In this review, we discuss how mitochondrial bioenergetics and reactive oxygen species production is impacted by dietary interventions that change nutrient availability and impact on aging, such as calorie restriction. We also discuss how dietary interventions alter mitochondrial Ca2+ transport, regulating both mitochondrial and cytosolic processes modulated by this ion. Overall, a plethora of literature data support the idea that mitochondrial oxidants and calcium transport act as integrating signals coordinating the response to changes in nutritional supply and demand in cells, tissues, and animals.
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.04.234
  8. Mol Pharm. 2024 May 02.
    Treg-Derived Extracellular Vesicles: Roles in Diseases and Theranostics.
    Tingting Wu, Lulu Wang, Chen Gao, Chen Jian, Yajing Liu, Zhiwen Fu, Chen Shi.
      Regulatory T cells (Tregs), a subset of CD4+ T cells, are indispensable in maintaining immune self-tolerance and have been utilized in various diseases. Treg-derived extracellular vesicles (Treg-EVs) have been discovered to play an important role in the mechanism of Treg functions. As cell-derived membranous particles, EVs carry multiple bioactive substances that possess tremendous potential for theranostics. Treg-EVs are involved in numerous physiological and pathological processes, carrying proteins and miRNAs inherited from the parental cells. To comprehensively understand the function of Treg-EVs, here we reviewed the classification of Treg-EVs, the active molecules in Treg-EVs, their various applications in diseases, and the existing challenges for Treg-EVs based theranostics. This Review aims to clarify the feasibility and potential of Treg-EVs in diseases and theranostics, facilitating further research and application of Treg-EVs.
    Keywords:  exosomes; extracellular vesicles; microvesicles; regulatory T cells; theranostics
    DOI:  https://doi.org/10.1021/acs.molpharmaceut.4c00233
  9. Redox Biol. 2024 Apr 29. pii: S2213-2317(24)00152-6. [Epub ahead of print]73 103174
    The absence of the ribosomal protein Rpl2702 elicits the MAPK-mTOR signaling to modulate mitochondrial morphology and functions.
    Ling Liu, Yifan Wu, Ke Liu, Mengdan Zhu, Shouhong Guang, Fengsong Wang, Xing Liu, Xuebiao Yao, Jiajia He, Chuanhai Fu.
      Ribosomes mediate protein synthesis, which is one of the most energy-demanding activities within the cell, and mitochondria are one of the main sources generating energy. How mitochondrial morphology and functions are adjusted to cope with ribosomal defects, which can impair protein synthesis and affect cell viability, is poorly understood. Here, we used the fission yeast Schizosaccharomyces Pombe as a model organism to investigate the interplay between ribosome and mitochondria. We found that a ribosomal insult, caused by the absence of Rpl2702, activates a signaling pathway involving Sty1/MAPK and mTOR to modulate mitochondrial morphology and functions. Specifically, we demonstrated that Sty1/MAPK induces mitochondrial fragmentation in a mTOR-independent manner while both Sty1/MAPK and mTOR increases the levels of mitochondrial membrane potential and mitochondrial reactive oxygen species (mROS). Moreover, we demonstrated that Sty1/MAPK acts upstream of Tor1/TORC2 and Tor1/TORC2 and is required to activate Tor2/TORC1. The enhancements of mitochondrial membrane potential and mROS function to promote proliferation of cells bearing ribosomal defects. Hence, our study reveals a previously uncharacterized Sty1/MAPK-mTOR signaling axis that regulates mitochondrial morphology and functions in response to ribosomal insults and provides new insights into the molecular and physiological adaptations of cells to impaired protein synthesis.
    Keywords:  MAPK; Mitochondria; Ribosome; Schizosaccharomyces pombe; mTOR
    DOI:  https://doi.org/10.1016/j.redox.2024.103174
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