Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies

Grumati, Paolo; Bonaldo, Paolo

doi:10.3390/cells1030325

Cited by 70 publications

(62 citation statements)

References 98 publications

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“…Adipocyte-specific role of BNIP3 in enhancement of mitochondrial bioenergetics Originally, BNIP3 was reported to impair mitochondrial bioenergetics, as there were defects in mtDNA and ATP production in myocytes [30,31]. However, our data show that BNIP3 enhances mitochondrial bioenergetics during rosiglitazone treatment, at least in adipocytes.…”

Section: Discussioncontrasting

(Expert classified)

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

Choi

Kim

et al. 2015

Diabetologia

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Aims/hypothesis Adipose tissue is a highly versatile system in which mitochondria in adipocytes undergo significant changes during active tissue remodelling. BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) is a mitochondrial protein and a known mitochondrial quality regulator. In this study, we investigated the role of BNIP3 in adipocytes, specifically under conditions of peroxisome proliferator-activated receptor-γ (PPARγ)-induced adipose tissue remodelling. Methods The expression of BNIP3 was evaluated in 3T3-L1 adipocytes in vitro, C57BL/6 mice fed a high-fat diet and db/db mice in vivo. Mitochondrial bioenergetics was investigated in BNIP3-knockdown adipocytes after rosiglitazone treatment. A putative peroxisome proliferator hormone responsive element (PPRE) was characterised by promoter assay and electrophoretic mobility shift assay (EMSA). ResultsThe protein BNIP3 was more abundant in brown adipose tissue than white adipose tissue. Furthermore, BNIP3 expression was upregulated by 3T3-L1 pre-adipocyte differentiation, starvation and rosiglitazone treatment. Conversely, BNIP3 expression in adipocytes decreased under various conditions associated with insulin resistance. This downregulation of BNIP3 was restored by rosiglitazone treatment. Knockdown of BNIP3 in adipocytes inhibited rosiglitazoneinduced mitochondrial biogenesis and function, partially mediated by the 5′ AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor γ, co-activator 1 α (PGC1α) signalling pathway. Rosiglitazone treatment increased the transcription level of Bnip3 in the reporter assay and the presence of the PPRE site in the Bnip3 promoter was demonstrated by EMSA. Conclusions/interpretation The protein BNIP3 contributes to the improvement of mitochondrial bioenergetics that occurs

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Section: Discussioncontrasting

(Expert classified)

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

Choi

Kim

et al. 2015

Diabetologia

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“…In parallel to the pronounced myopathy, the mitochondria of aged AMPK-MKO mice have an aberrant enlarged morphology and an increased amount of mtDNA deletions, indicative of accelerated mitochondrial dysfunction. This mitochondrial phenotype of aged AMPK-MKO mice resembles effects seen in TSC-1-deficient mice, which have chronically impaired autophagy due to hyperactivation of mTORC1 (Castets et al, 2013) and with muscular dystrophy (Grumati and Bonaldo, 2012).…”

Section: Discussionmentioning

confidence: 95%

AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging

et al. 2015

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The AMP-activated protein kinase (AMPK) activates autophagy, but its role in aging and fasting-induced muscle function has not been defined. Here we report that fasting mice lacking skeletal muscle AMPK (AMPK-MKO) results in hypoglycemia and hyperketosis. This is not due to defective fatty acid oxidation, but instead is related to a block in muscle proteolysis that leads to reduced circulating levels of alanine, an essential amino acid required for gluconeogenesis. Markers of muscle autophagy including phosphorylation of Ulk1 Ser555 and Ser757 and aggregation of RFP-LC3 puncta are impaired. Consistent with impaired autophagy, aged AMPK-MKO mice possess a significant myopathy characterized by reduced muscle function, mitochondrial disease, and accumulation of the autophagy/mitophagy proteins p62 and Parkin. These findings establish an essential requirement for skeletal muscle AMPK-mediated autophagy in preserving blood glucose levels during prolonged fasting as well as maintaining muscle integrity and mitochondrial function during aging.

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“…Pertinent for maintaining skeletal muscle homeostasis [101], collagen VI has also been implicated in autophagic and mitochondrial regulation [102–104]. Loss of collagen VI (e.g.…”

Section: The Instructive Role Of Decorin In Autophagy and Tumorigementioning

confidence: 99%

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

Theocharis

Skandalis

Neill

et al. 2015

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

114

127

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Proteoglycans control numerous normal and pathological processes, among which are morphogenesis, tissue repair, inflammation, vascularization and cancer metastasis. During tumor development and growth, proteoglycan expression is markedly modified in the tumor microenvironment. Altered expression of proteoglycans on tumor and stromal cell membranes affects cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Despite the high complexity and heterogeneity of breast cancer, the rapid evolution in our knowledge that proteoglycans are among the key players in the breast tumor microenvironment suggests their potential as pharmacological targets in this type of cancer. It has been recently suggested that pharmacological treatment may target proteoglycan metabolism, their utilization as targets for immunotherapy or their direct use as therapeutic agents. The diversity inherent in the proteoglycans that will be presented herein provides the potential for multiple layers of regulation of breast tumor behavior. This review summarizes recent developments concerning the biology of selected proteoglycans in breast cancer, and presents potential targeted therapeutic approaches based on their novel key roles in breast cancer.

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Autophagy in Skeletal Muscle Homeostasis and in Muscular Dystrophies

Cited by 70 publications

References 98 publications

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

BNIP3 is essential for mitochondrial bioenergetics during adipocyte remodelling in mice

AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging

Insights into the key roles of proteoglycans in breast cancer biology and translational medicine

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