Mitochondria in Liver Regeneration: Energy Metabolism and Posthepatectomy Liver Dysfunction

Alexandrino, Henrique; Rolo, Anabela P.; Tralhão, José Guilherme; Sousa, F. Castro e; Palmeira, Carlos M.

doi:10.1007/978-3-319-73344-9_8

Cited by 8 publications

(10 citation statements)

References 151 publications

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“…These are linked to mitochondrial dysfunction and increase the risk of suffering from posthepatectomy liver failure as they severely limit liver regeneration and exacerbate the susceptibility to IRI. [ 31 ] Therefore, we examined whether MCJ silencing could reduce the susceptibility of steatotic or old livers to IRI and enhance liver regeneration.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

Goikoetxea‐Usandizaga

Serrano‐Maciá

Delgado

et al. 2021

Hepatology

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Background and Aims: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models.

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Section: Resultsmentioning

confidence: 99%

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

Goikoetxea‐Usandizaga

Serrano‐Maciá

Delgado

et al. 2021

Hepatology

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“…Liver regeneration requires abundant energy and cellular substances for DNA replication and cell division [23]. Autophagy can effectively provide the needed substances during the regenerative period and remove dysfunctional organelles or aggregated proteins [11,13].…”

Section: Impaired Regeneration Of the Aged Liver Is Related To Impairmentioning

confidence: 99%

“…It is well known that liver regeneration requires abundant ATP to support the energy-consuming process of cell division and growth [23]. Hepatocytes are rich in mitochondria to meet the energy needs such as their multitudinous metabolic activities and liver regeneration.…”

Section: Autophagy Provides Energy As Needed For Liver Regenerationmentioning

confidence: 99%

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The Role of Autophagy for the Regeneration of the Aging Liver

Hua

Tautenhahn

et al. 2020

IJMS

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Age is one of the key risk factors to develop malignant diseases leading to a high incidence of hepatic tumors in the elderly population. The only curative treatment for hepatic tumors is surgical removal, which initiates liver regeneration. However, liver regeneration is impaired with aging, leading to an increased surgical risk for the elderly patient. Due to the increased risk, those patients are potentially excluded from curative surgery. Aging impairs autophagy via lipofuscin accumulation and inhibition of autophagosome formation. Autophagy is a recycling mechanism for eukaryotic cells to maintain homeostasis. Its principal function is to degrade endogenous bio-macromolecules for recycling cellular substances. A number of recent studies have shown that the reduced regenerative capacity of the aged remnant liver can be restored by promoting autophagy. Autophagy can be activated via multiple mTOR-dependent and mTOR-independent pathways. However, inducing autophagy through the mTOR-dependent pathway alone severely impairs liver regeneration. In contrast, recent observations suggest that inducing autophagy via mTOR-independent pathways might be promising in promoting liver regeneration. Conclusion: Activation of autophagy via an mTOR-independent autophagy inducer is a potential therapy for promoting liver regeneration, especially in the elderly patients at risk.

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“…Liver regeneration is an energy-intensive process. The division and growth of hepatocytes require abundant energy supply [ 256 ]. Hepatocytes are rich in mitochondria, but liver resection can cause substantial mitochondrial damage and decrease hepatocyte ATP synthesis.…”

Section: Impaired Liver Regenerationmentioning

confidence: 99%

Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver

Tautenhahn

Dirsch

et al. 2021

Oxidative Medicine and Cellular Longevity

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Aging is a natural life process which leads to a gradual decline of essential physiological processes. For the liver, it leads to alterations in histomorphology (steatosis and fibrosis) and function (protein synthesis and energy generation) and affects central hepatocellular processes (autophagy, mitochondrial respiration, and hepatocyte proliferation). These alterations do not only impair the metabolic capacity of the liver but also represent important factors in the pathogenesis of malignant liver disease. Autophagy is a recycling process for eukaryotic cells to degrade dysfunctional intracellular components and to reuse the basic substances. It plays a crucial role in maintaining cell homeostasis and in resisting environmental stress. Emerging evidence shows that modulating autophagy seems to be effective in improving the age-related alterations of the liver. However, autophagy is a double-edged sword for the aged liver. Upregulating autophagy alleviates hepatic steatosis and ROS-induced cellular stress and promotes hepatocyte proliferation but may aggravate hepatic fibrosis. Therefore, a well-balanced autophagy modulation strategy might be suitable to alleviate age-related liver dysfunction. Conclusion. Modulation of autophagy is a promising strategy for “rejuvenation” of the aged liver. Detailed knowledge regarding the most devastating processes in the individual patient is needed to effectively counteract aging of the liver without causing obvious harm.

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Mitochondria in Liver Regeneration: Energy Metabolism and Posthepatectomy Liver Dysfunction

Cited by 8 publications

References 151 publications

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

The Role of Autophagy for the Regeneration of the Aging Liver

Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver

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