Electrophilic Aldehyde 4-Hydroxy-2-Nonenal Mediated Signaling and Mitochondrial Dysfunction

被引:41
作者
Sharma, Sudha [1 ]
Sharma, Papori [1 ]
Bailey, Tara [1 ]
Bhattarai, Susmita [1 ]
Subedi, Utsab [1 ]
Miller, Chloe [1 ]
Ara, Hosne [1 ]
Kidambi, Srivatsan [2 ]
Sun, Hong [1 ]
Panchatcharam, Manikandan [1 ]
Miriyala, Sumitra [1 ]
机构
[1] Louisiana State Univ, Hlth Sci Ctr, Dept Cellular Biol & Anat, Shreveport, LA 71103 USA
[2] Univ Nebraska, Dept Chem & Biomol Engn, Lincoln, NB 68588, Canada
基金
美国国家卫生研究院;
关键词
oxidative stress; lipid peroxidation; 4-hydroxynonenal; mitochondrial dysfunction; LIPID-PEROXIDATION PRODUCT; OXIDATIVE STRESS; 4-HYDROXYNONENAL; 4-HNE; CARDIOVASCULAR-DISEASE; N-ACETYLCYSTEINE; FOCAL ADHESION; KEY MOLECULE; CELL-CYCLE; METABOLISM; APOPTOSIS;
D O I
10.3390/biom12111555
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reactive oxygen species (ROS), a by-product of aerobic life, are highly reactive molecules with unpaired electrons. The excess of ROS leads to oxidative stress, instigating the peroxidation of polyunsaturated fatty acids (PUFA) in the lipid membrane through a free radical chain reaction and the formation of the most bioactive aldehyde, known as 4-hydroxynonenal (4-HNE). 4-HNE functions as a signaling molecule and toxic product and acts mainly by forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and lipids. The mitochondria have been implicated as a site for 4-HNE generation and adduction. Several studies clarified how 4-HNE affects the mitochondria's functions, including bioenergetics, calcium homeostasis, and mitochondrial dynamics. Our research group has shown that 4-HNE activates mitochondria apoptosis-inducing factor (AIFM2) translocation and facilitates apoptosis in mice and human heart tissue during anti-cancer treatment. Recently, we demonstrated that a deficiency of SOD2 in the conditional-specific cardiac knockout mouse increases ROS, and subsequent production of 4-HNE inside mitochondria leads to the adduction of several mitochondrial respiratory chain complex proteins. Moreover, we highlighted the physiological functions of HNE and discussed their relevance in human pathophysiology and current discoveries concerning 4-HNE effects on mitochondria.
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页数:16
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