Dear Editor,Lipid droplets(LDs)are dynamic lipid-storage organelles of storage depots and sources of essential substrates for myriad cellular processes and protect cells from lipotoxicity(Ohsaki et al.,2006).Disrupted...Dear Editor,Lipid droplets(LDs)are dynamic lipid-storage organelles of storage depots and sources of essential substrates for myriad cellular processes and protect cells from lipotoxicity(Ohsaki et al.,2006).Disrupted LD and fat storage homeostasis has been linked to metabolic diseases such as atherosclerosis,obesity,and type II diabetes(Levin et al.,2001).Structurally,the core of neutral lipids in LDs is surroun ded by a phospholipid mono layer and coated with specific proteins(Storey et al.,2011).Perilipin family of proteins are the predominant LD-associated proteins.展开更多
Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics(gentamicin,amikacin,neomycin)and platinum anti-tumor drugs(cisplatin,carboplatin).The inner ear and kidney share similar...Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics(gentamicin,amikacin,neomycin)and platinum anti-tumor drugs(cisplatin,carboplatin).The inner ear and kidney share similarities in drug deposition and toxicity,but the underlying pathophysiological mechanisms remain unclear.Investigating the shared mechanisms and metabolic alterations in these distinct organs will provide valuable insights for clinical therapy.A strong correlation has been identified between the spatiotemporal accumulation patterns of neomycin and the specific occurrence of lipid metabolism disorders in these two organs.The primary allocation of neomycin to mitochondria results in a notable escalation in the accumulation of lipid droplets(LDs)and more interactions between mitochondria and LDs,leading to a sequence of disturbances in lipid metabolism,such as increased lipid ROS and the blocked transfer of fatty acids from LDs to mitochondria.PGC-1αdeficiency worsens the neomycin-induced disorders in lipid metabolism and intensifies the pathological interactions between mitochondria and LDs,as indicated by the exacerbated disturbance of dynamic LD turnover,increased level of oxidized lipids and decreased use of fatty acids.This investigation provides a fresh perspective on the lipid metabolic dysfunction related to mitochondria-LD interactions in drug-induced ototoxicity and nephrotoxicity,potentially providing novel avenues for intervention strategies.展开更多
基金the National Key Research and Development Program of China(2017YFA0102801,2018YFA0107 003)National Natural Science Foundation of China(Grant Nos.91640119,91749113,81330055,31570827 and 31871479)+6 种基金Guangzhou Science and Technology Project(201605030012)Natural Science Foundation of Guangdong Province(2017A03031 3116)Guangdong Science and Technology Department Planning Project(2015B020228002)the NIH(HL131744 and CA211653)the Welch Foundation(Q-1673 and I-1441)CPRITRP160462the C-BASS Shared Resource at the Dan L.Duncan Cancer Center(DLDCC)of Baylor College of Medicine(P30CA125123).
文摘Dear Editor,Lipid droplets(LDs)are dynamic lipid-storage organelles of storage depots and sources of essential substrates for myriad cellular processes and protect cells from lipotoxicity(Ohsaki et al.,2006).Disrupted LD and fat storage homeostasis has been linked to metabolic diseases such as atherosclerosis,obesity,and type II diabetes(Levin et al.,2001).Structurally,the core of neutral lipids in LDs is surroun ded by a phospholipid mono layer and coated with specific proteins(Storey et al.,2011).Perilipin family of proteins are the predominant LD-associated proteins.
基金supported by the National Natural Science Foundation of China(82274014,82330033,82030029,92149304,82101228)the Leading Technology Foundation Research Project of Jiangsu Province(BK20192005,China)+1 种基金National Key R&D Program of China(Nos.2021YFA1101300,2021YFA1101800,and 2020YFA0112503)the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ202302,China).
文摘Ototoxicity and nephrotoxicity are the most prevalent side effects of aminoglycoside antibiotics(gentamicin,amikacin,neomycin)and platinum anti-tumor drugs(cisplatin,carboplatin).The inner ear and kidney share similarities in drug deposition and toxicity,but the underlying pathophysiological mechanisms remain unclear.Investigating the shared mechanisms and metabolic alterations in these distinct organs will provide valuable insights for clinical therapy.A strong correlation has been identified between the spatiotemporal accumulation patterns of neomycin and the specific occurrence of lipid metabolism disorders in these two organs.The primary allocation of neomycin to mitochondria results in a notable escalation in the accumulation of lipid droplets(LDs)and more interactions between mitochondria and LDs,leading to a sequence of disturbances in lipid metabolism,such as increased lipid ROS and the blocked transfer of fatty acids from LDs to mitochondria.PGC-1αdeficiency worsens the neomycin-induced disorders in lipid metabolism and intensifies the pathological interactions between mitochondria and LDs,as indicated by the exacerbated disturbance of dynamic LD turnover,increased level of oxidized lipids and decreased use of fatty acids.This investigation provides a fresh perspective on the lipid metabolic dysfunction related to mitochondria-LD interactions in drug-induced ototoxicity and nephrotoxicity,potentially providing novel avenues for intervention strategies.
