Muscle-generated BDNF (brain derived neurotrophic factor) maintains mitochondrial quality control in female mice

被引：68

作者：

Ahuja, Palak ^{[1
]}

Ng, Chun Fai ^{[1
]}

Pang, Brian Pak Shing ^{[1
]}

Chan, Wing Suen ^{[1
]}

Tse, Margaret Chui Ling ^{[2
]}

Bi, Xinyi ^{[1
]}

Kwan, Hiu-Lam Rachel ^{[2
]}

Brobst, Daniel ^{[3
]}

Herlea-Pana, Oana ^{[3
]}

Yang, Xiuying ^{[4
,5
]}

Du, Guanhua ^{[4
,5
]}

Saengnipanthkul, Suchaorn ^{[6
]}

Noh, Hye Lim ^{[6
]}

Jiao, Baowei ^{[7
]}

Kim, Jason K. ^{[6
,8
]}

Lee, Chi Wai ^{[2
]}

Ye, Keqiang ^{[9
]}

Chan, Chi Bun ^{[1
,10
]}

机构：

[1] Univ Hong Kong, Sch Biol Sci, 5N10 Kadoorie Biol Sci Bldg,Pokfulam Rd, Hong Kong, Peoples R China

[2] Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci, Hong Kong, Peoples R China

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK USA

[4] Peking Union Med Coll, State Key Lab Bioact Subst & Funct Nat Med, Inst Mat Med, Beijing, Peoples R China

[5] Peking Union Med Coll, Beijing Key Lab Drug Target & Screening Res, Inst Mat Med, Beijing, Peoples R China

[6] Univ Massachusetts, Med Sch, Program Mol Med, Worcester, MA 01605 USA

[7] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Yunnan, Peoples R China

[8] Univ Massachusetts, Div Endocrinol Metab & Diabet, Dept Med, Med Sch, Worcester, MA 01605 USA

[9] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA

[10] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Hong Kong, Peoples R China

来源：

AUTOPHAGY | 2022年 / 18卷 / 06期

关键词：

BDNF; mitochondria; mitophagy; muscle; obesity; DEPENDENT PROTEIN-KINASE; SKELETAL-MUSCLE; INSULIN-RESISTANCE; UPSTREAM KINASE; PHOSPHORYLATION; ACTIVATION; MITOPHAGY; DYSFUNCTION; BIOGENESIS; EXPRESSION;

D O I：

10.1080/15548627.2021.1985257

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism is not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance in skeletal muscle via the PRKAA/AMPK-PINK1-PRKN/Parkin and PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression in myotubes reduced fatty acid-induced mitofission and mitophagy, which was associated with mitochondrial elongation and impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice displayed defective mitofission and mitophagy, and accumulation of dysfunctional mitochondria in the muscle when they were fed with a high-fat diet (HFD). These animals also have exacerbated body weight gain, increased intramyocellular lipid deposition, reduced energy expenditure, poor metabolic flexibility, and more insulin resistance. In contrast, consuming a BDNF mimetic (7,8-dihydroxyflavone) increased mitochondrial content, and enhanced mitofission and mitophagy in the skeletal muscles. Hence, BDNF is an essential myokine to maintain mitochondrial quality and function, and its repression in obesity might contribute to impaired metabolism.

引用

页码：1367 / 1384

页数：18

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