Increased mitochondrial Ca2+ contributes to health decline with age and Duchene muscular dystrophy in C. elegans

被引：11

作者：

Higashitani, Atsushi ^{[1
,8
]}

Teranishi, Mika ^{[1
]}

Nakagawa, Yui ^{[1
]}

Itoh, Yukou ^{[1
]}

Sudevan, Surabhi ^{[2
]}

Szewczyk, Nathaniel J. ^{[2
,3
]}

Kubota, Yukihiko ^{[4
]}

Abe, Takaaki ^{[5
,6
]}

Kobayashi, Takeshi ^{[7
,9
]}

机构：

[1] Tohoku Univ, Grad Sch Life Sci, Sendai, Japan

[2] Univ Nottingham, Royal Derby Hosp, Ctr Musculoskeletal Ageing Res, Med Res Council MRC Versus Arthrit, Derby, England

[3] Ohio Univ, Heritage Coll Osteopath Med, Ohio Musculoskeletal & Neurol Inst, Athens, OH USA

[4] Ritsumeikan Univ, Coll Life Sci, Kusatsu, Japan

[5] Tohoku Univ, Grad Sch Biomed Engn, Div Med Sci, Sendai, Japan

[6] Tohoku Univ, Grad Sch Med, Dept Clin Biol & Hormonal Regulat, Sendai, Japan

[7] Nagoya Univ, Grad Sch Med, Nagoya, Japan

[8] Tohoku Univ, Grad Sch Life Sci, Sendai 9808577, Japan

[9] Nagoya Univ, Grad Sch Med, Nagoya 4668550, Japan

来源：

FASEB JOURNAL | 2023年 / 37卷 / 04期

基金：

英国生物技术与生命科学研究理事会; 日本学术振兴会;

关键词：

aging; calcium; dystrophy; MCU; mitophagy; sarcopenia; CALCIUM; INDICATORS; SARCOPENIA; TRANSPORT; PROTEIN;

D O I：

10.1096/fj.202201489RR

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：

Sarcopenia is a geriatric syndrome characterized by an age-related decline in skeletal muscle mass and strength. Here, we show that suppression of mitochondrial calcium uniporter (MCU)-mediated Ca2+ influx into mitochondria in the body wall muscles of the nematode Caenorhabditis elegans improved the sarcopenic phenotypes, blunting movement and mitochondrial structural and functional decline with age. We found that normally aged muscle cells exhibited elevated resting mitochondrial Ca2+ levels and increased mitophagy to eliminate damaged mitochondria. Similar to aging muscle, we found that suppressing MCU function in muscular dystrophy improved movement via reducing elevated resting mitochondrial Ca2+ levels. Taken together, our results reveal that elevated resting mitochondrial Ca2+ levels contribute to muscle decline with age and muscular dystrophy. Further, modulation of MCU activity may act as a potential pharmacological target in various conditions involving muscle loss.

引用

页数：15

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