Mitochondrial dynamics and morphology in beta-cells

Stiles, Linsey; Shirihai, Orian S.

doi:10.1016/j.beem.2012.05.004

Cited by 66 publications

(60 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because insulin-secreting cell lines differ between themselves and by comparison with primary beta cells in terms of their metabolomics, this argues in favour of feedback mechanisms that adjust FIS1 expression to the current need for mitochondrial network regulation in a given cell population. Adaptation of mitochondrial dynamics may rely on the mutual regulation of fusion and fission genes (Stiles & Shirihai 2012). Moreover, the influence of cell morphology and formation of cell-cell contacts on glucose responsiveness and mitochondrial network appearance should be considered as an independent effect.…”

Section: Discussionmentioning

confidence: 99%

“…Maintenance of a functional mitochondrial network requires these nuclear encoded proteins to act in concert with each other and with cellular ionic and second messenger systems, a process that is still imperfectly understood (Hyde et al 2010). It is assumed that FIS1 initiates mitochondrial fission via oligomerisation in the outer mitochondrial membrane and eventually triggers the mitochondrial life cycle (Serasinghe & Yoon 2008, Stiles & Shirihai 2012. In Saccharomyces cerevisiae yeast, complex formation of Fis1 and Drp1 on the outer mitochondrial membrane is mediated by Mdv1, a protein that is not expressed in mammals (Stojanovski et al 2004, Wells et al 2007, Zhang & Chan 2007.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Precise expression of Fis1 is important for glucose responsiveness of beta cells

Schultz

Waterstradt

Kantowski

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

Mitochondrial network functionality is vital for glucose-stimulated insulin secretion in pancreatic beta cells. Altered mitochondrial dynamics in pancreatic beta cells are thought to trigger the development of type 2 diabetes mellitus. Fission protein 1 (Fis1) might be a key player in this process. Thus, the aim of this study was to investigate mitochondrial morphology in dependence of beta cell function, after knockdown and overexpression of Fis1. We demonstrate that glucose-unresponsive cells with impaired glucose-stimulated insulin secretion (INS1-832/2) showed decreased mitochondrial dynamics compared with glucose-responsive cells (INS1-832/13). Accordingly, mitochondrial morphology visualised using MitoTracker staining differed between the two cell lines. INS1-832/2 cells formed elongated and clustered mitochondria, whereas INS1-832/13 cells showed a homogenous mitochondrial network. Fis1 overexpression using lentiviral transduction significantly improved glucose-stimulated insulin secretion and mitochondrial network homogeneity in glucose-unresponsive cells. Conversely, Fis1 downregulation by shRNA, both in primary mouse beta cells and glucose-responsive INS1-832/13 cells, caused unresponsiveness and significantly greater numbers of elongated mitochondria. Overexpression of FIS1 in primary mouse beta cells indicated an upper limit at which higher FIS1 expression reduced glucose-stimulated insulin secretion. Thus, FIS1 was overexpressed stepwise up to a high concentration in RINm5F cells using the RheoSwitch system. Moderate FIS1 expression improved glucose-stimulated insulin secretion, whereas high expression resulted in loss of glucose responsiveness and in mitochondrial artificial loop structures and clustering. Our data confirm that FIS1 is a key regulator in pancreatic beta cells, because both glucosestimulated insulin secretion and mitochondrial dynamics were clearly adapted to precise expression levels of this fission protein. 230:1Mitochondrial dynamics and insulin secretion j schultz and others

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Precise expression of Fis1 is important for glucose responsiveness of beta cells

Schultz

Waterstradt

Kantowski

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…13 Accumulation of damaged mitochondria is prevented by their continuous fission and fusion which permits the segregation and clearance of dysfunctional mitochondria through mitophagy. 47 Thus, it is not surprising that cells with high energy demands such as cones would rely heavily on mitophagy as their increased metabolism and ATP requirements would produce excess ROS potentially damaging their mitochondria. Our observation that the earliest feature of ATG5-deficiency in cones was www.tandfonline.comthe accumulation of damaged mitochondria in the inner segments supports this idea.…”

Section: Discussionmentioning

confidence: 99%

Autophagy supports color vision

et al. 2015

View full text Add to dashboard Cite

Abbreviations: AMD, age-related macular degeneration; AMPK, AMP-activated protein kinase; ATG5, autophagy-related 5; CIS, cone inner segment; COS, cone outer segment; ERG, electroretinogram; GFP, green fluorescent protein; LC3B, microtubule-associated protein 1 light chain 3 b; LCA, Leber's congenital amaurosis; L/D, 12 h light/12 h dark; ONL, outer nuclear layer; OS, outer segment; p-AMPK, phosphorylated AMPK; PARK2/Parkin, parkin RBR ubiquitin protein ligase; PFA, paraformaldehyde; PINK1, PTEN-induced putative kinase 1; PNA, peanut agglutinin; ROS, reactive oxygen species; RP, retinitis pigmentosa; TEM, transmission electron microscopy; TOMM20/TOM20, translocase of outer mitochondrial membrane 20 homolog (yeast)Cones comprise only a small portion of the photoreceptors in mammalian retinas. However, cones are vital for color vision and visual perception, and their loss severely diminishes the quality of life for patients with retinal degenerative diseases. Cones function in bright light and have higher demand for energy than rods; yet, the mechanisms that support the energy requirements of cones are poorly understood. One such pathway that potentially could sustain cones under basal and stress conditions is macroautophagy. We addressed the role of macroautophagy in cones by examining how the genetic block of this pathway affects the structural integrity, survival, and function of these neurons. We found that macroautophagy was not detectable in cones under normal conditions but was readily observed following 24 h of fasting. Consistent with this, starvation induced phosphorylation of AMPK specifically in cones indicating cellular starvation. Inhibiting macroautophagy in cones by deleting the essential macroautophagy gene Atg5 led to reduced cone function following starvation suggesting that cones are sensitive to systemic changes in nutrients and activate macroautophagy to maintain their function. ATG5-deficiency rendered cones susceptible to lightinduced damage and caused accumulation of damaged mitochondria in the inner segments, shortening of the outer segments, and degeneration of all cone types, revealing the importance of mitophagy in supporting cone metabolic needs. Our results demonstrate that macroautophagy supports the function and long-term survival of cones providing for their unique metabolic requirements and resistance to stress. Targeting macroautophagy has the potential to preserve cone-mediated vision during retinal degenerative diseases.

show abstract

“…1) [1,[3][4][5]. Because mitochondrial function is crucial for pancreatic beta cell stimulus-secretion coupling, mitochondrial network failure is capable of promoting hyperglycaemia [1,6].…”

Section: Mitochondrial Shape and Functionmentioning

confidence: 99%

Mitochondrial network regulation and its potential interference with inflammatory signals in pancreatic beta cells

Baltrusch

2016

Diabetologia

View full text Add to dashboard Cite

Mitochondria fulfil multiple tasks in nutrient metabolism, energy production, redox homeostasis and stress response, and are essential for pancreatic beta cell function. The dynamism and health of the mitochondrial network is regulated by fission-and fusion-triggering factors and by a quality control system that removes dysfunctional organelles. Alongside the role of mitochondria in regulating apoptotic cell death mediated primarily via production of reactive oxygen species and release of cytochrome c, there is evidence of other links between mitochondria and inflammation that have implications for cell viability. This review briefly outlines two pathways that are potentially vital for pancreatic beta cell function. The first concerns the regulation of Parkin, a protein that acts, not only as a central player in regulating mitophagy, but also as an activator of the NF-ĸB pathway. The fact that expression of optic atrophy protein 1 (OPA1), a mitochondrial fusion inducer and master mitochondrial cristae biogenetic factor, is increased following NF-ĸB activation highlights a point of mitochondrial control that might be influenced by TNFα signalling. A second axis of interest is suggested by IL-6-mediated upregulation of the fission inducer FIS1 alongside downregulation of mitofusin 2 (MFN2), a guard of mitochondrial fusion and metabolism and an inhibitor of apoptosis. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied two other reviews on topics from this symposium (by Marc Donath,

show abstract

Mitochondrial dynamics and morphology in beta-cells

Cited by 66 publications

References 65 publications

Precise expression of Fis1 is important for glucose responsiveness of beta cells

Precise expression of Fis1 is important for glucose responsiveness of beta cells

Autophagy supports color vision

Mitochondrial network regulation and its potential interference with inflammatory signals in pancreatic beta cells

Contact Info

Product

Resources

About