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Therapeutic regulation of autophagy in hepatic metabolism

Acta Pharmaceutica Sinica B 2022年第1期12卷 33-49页

作者： Katherine Byrnes Sophia Blessinger Niani Tiaye Bailey Russell Scaife Gang Liu bilon khambu Department of Pathology and Laboratory Medicine Tulane University School of MedicineNew OrleansLA 70112USA

Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ thatgoverns body energy metabolism. Autophagy’s role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders.

关键词： Autophagy Liver metabolism Signaling proteins Lysosome Nutrient regeneration Quality control Farnesoid X receptor Cryptochrome 1

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Hepatic senescence, the good and the bad

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World Journal of Gastroenterology 2019年第34期25卷 5069-5081页

作者： Nazmul Huda Gang Liu Honghai Hong Shengmin Yan bilon khambu Xiao-Ming Yin Department of Pathology and Laboratory Medicine Indiana University School of MedicineIndianapolis

Gradual alterations of cell’s physiology and functions due to age or exposure to various stresses lead to the conversion of normal cells to senescent *** becoming senescent,the cell stops dividing permanently but remains metabolically *** senescence does not have a single marker but is characterized mainly by a combination of multiple markers,such as,morphological changes,expression of cell cycle inhibitors,senescence associatedβ-galactosidase activity,and changes in nuclear *** cells in an organ become senescent,the entire organism can be *** may occur through the senescence-associated secretory phenotype(SASP).SASP may exert beneficial or harmful effects on the microenvironment of *** on senescence has become a very exciting field in cell biology since the link between age-related diseases,including cancer,and senescence has been *** loss of regenerative and homeostatic capacity of the liver over the age is somehow connected to cellular *** major contributors of senescence properties in the liver are hepatocytes and *** cells in the liver have been implicated in the etiology of chronic liver diseases including cirrhosis and hepatocellular carcinoma and in the interference of liver *** review summarizes recently reported findings in the understanding of the molecular mechanisms of senescence and its relationship with liver diseases.

关键词： Senescence Senescence associated secretory phenotype Hepatocyte Cholangiocyte Hepatic stellate cell Cell cycle arrest DNA damage

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Autophagy in non-alcoholic fatty liver disease and alcoholic liver disease

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Liver Research 2018年第3期2卷 112-119页

作者： bilon khambu Shengmin Yan Nazmul Huda Gang Liu Xiao-Ming Yin Department of Pathology and Laboratory Medicine Indiana University School of MedicineIndianapolisINUSA

Autophagy is an evolutionarily conserved intracellular degradative function that is important for liver *** evidence suggests that autophagy is deregulated during the progression and development of alcoholic and non-alcoholic liver *** autophagy prevents the clearance of excessive lipid droplets(LDs),damaged mitochondria,and toxic protein aggregates,which can be generated during the progression of various liver diseases,thus contributing to the development of steatosis,injury,steatohepatitis,fibrosis,and *** this review,we look at the status of hepatic autophagy during the pathogenesis of alcoholic and non-alcoholic liver *** also examine the mechanisms of defects in autophagy,and the hepato-protective roles of autophagy in non-alcoholic fatty liver disease(NAFLD)and alcoholic liver disease(ALD),focusing mainly on steatosis and liver ***,we discuss the therapeutic potential of autophagy modulating agents for the treatment of these two common liver diseases.

关键词： Autophagy Non-alcoholic fatty liver disease(NAFLD) Alcoholic liver disease(ALD) Liver injury Steatosis

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Suppression of lysosomal function by small molecules can induce autophagy via mTORC1 inhibition

Suppression of lysosomal function by small molecules can ind...

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细胞—生命的基础——中国细胞生物学学会2013年全国学...

作者： Min Li Pei-Qing Liu Xiao-Yun Chen,School of Medicine bilon khambu,School of Medicine Hao Zhang,School of Medicine Xiao-Ming Yin,School of Medicine School of Pharmaceutical Sciences Department of Pharmacology and ToxicologySun Yet-Sen University School of Medicine Department of Pathology and Laboratory MedicineIndiana University

Autophagy is an evolutionarily conserved lysosome-dependent degradative process that intracellular material is degraded to fuel starving cells and eliminate intracellular *** accumulation of autophagosomes could be due to both induction of autophagy and inhibition of autophagosome *** first investigate that niclosamide acts not only as an autophagy inducer detected by

关键词： Autophagy Lysosome inhibitor Lysosome membrane permeabilization mTORC1

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