Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease

Abstract

Metabolic diseases, including obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD), are rising in both incidence and prevalence and remain a major global health and socioeconomic burden in the twenty-first century. Despite an increasing understanding of these diseases, the lack of effective treatments remains an ongoing challenge. Mitochondria are key players in intracellular energy production, calcium homeostasis, signaling, and apoptosis. Emerging evidence shows that mitochondrial dysfunction participates in the pathogeneses of metabolic diseases. Exogenous supplementation with healthy mitochondria is emerging as a promising therapeutic approach to treating these diseases. This article reviews recent advances in the use of mitochondrial transplantation therapy (MRT) in such treatment.

Mitochondrial Transfer as a Novel Therapeutic Approach in Disease Diagnosis and Treatment

“…Oxidative stress (OS), insulin resistance (IR), and metabolic diseases are all linked to mitochondrial dysfunction, and all three of these conditions-obesity, diabetes, and NAFLD-are on the rise [120]. Therefore, it is anticipated that the restoration of mitochondrial homeostasis will have a potential therapeutic effect on metabolic diseases and their complications [121]. Previously, Spees et al (2006) published the evidence of mitochondrial transmission between mammalian cells [10].…”

“…Uncertainties in culture method, donor cells, growth level, storage and shipping circumstances, and ethical sanction also limit MSCs' clinical utility. Platelets are a more desirable source for autologous mitochondrial transplantation due to their availability, abundance, and minimal immunogenicity [121]. However, Pang et al (2021) showed that therapeutic encouragement of mitochondrial transfers or mitochondrial transplantation is a viable therapy for disorders, such as heart stress, obesity, acute lung damage, and sepsis, since these conditions all include mitochondrial dysfunction (Figure 2) [74,130,135].…”

Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases

“…In addition, EVs are natural cell-derived drug carriers. EVs with a particle size larger than 200 nm, that is medium-to-large extracellular vesicles (m/lEVs) are naturally transported mitochondria during biogenesis to improve the survival rate of injured recipient tissues, and effectively protect mitochondrial integrity and activity, prolonging their life span in the blood, thus making EVs a promising carrier [ 65 ]. A recent study found that activation of PGC-1 α make m/lEVs carry a higher mitochondrial load, but it is often expensive and time-consuming [ 66 ].…”

“…Intercellular mitochondrial transmission can also be sensed by other cells, for example, the release of dysfunctional mitochondria in I/R injury was sensed by MSCs to enhance mitochondrial biogenesis as a negative feedback mechanism [ 53 ]. Intercellular mitochondrial transfer also rescued cellular injury by taking up functional mitochondria, thereby improving mitochondrial biogenesis [ 65 ].…”

Mitochondria Transplantation Mitigates Damage in an In Vitro Model of Renal Tubular Injury and in an Ex Vivo Model of DCD Renal Transplantation

“…13 As mitochondrial dysfunction is a common denominator in a myriad of pathologic conditions including renal IRI, isolated mitochondria transplantation (MITO) has recently emerged as a promising therapeutic approach. 10,15 In fact, rather than targeting a specific step of the above mentioned chain of events, MITO has been proposed to address irreversible mitochondrial damage by providing viable mitochondria isolated from a healthy source 10,13,[16][17][18][19][20] and data already exists on the application of this approach to treat renal ischemic damage. [21][22][23][24] In a clinically relevant model of IRI, damage was inflicted to the animals by occlusion of the renal arteries for 60 minutes.…”