Mitochondrial Morphology and Intracellular Calcium Homeostasis in Cytochrome Oxidase-Deficient Human Fibroblasts

Handran, Shawn D.; Werth, John; DeVivo, Darryl C.; Rothman, Steven M.

doi:10.1006/nbdi.1996.0125

Cited by 15 publications

(13 citation statements)

References 38 publications

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“…Importantly, these changes did not correlate with passage number (Table 1). This is in agreement with previous findings showing that mitochondrial morphology is independent of passage number in these cells (20). Recent work revealed a connection between cell cycle phase and mitochondrial structure in human osteosarcoma (143B) cells (34).…”

Section: Discussionsupporting

confidence: 85%

“…In contrast to earlier studies with human skin fibroblasts (5,19,20,25,35,52), the present study was aimed at a more quantitative analysis of mitochondrial shape and number. To this end, we applied our recently developed three-step protocol (28) for automated analysis of mitochondrial morphology.…”

Section: Automated Analysis Of Mitochondrial Shape and Number In Humamentioning

confidence: 96%

“…Earlier studies suggested that the efficiency of the OXPHOS system is somehow linked to mitochondrial shape and/or number (22). Alterations in mitochondrial number and shape are frequently encountered during mitochondrial and cellular dysfunction (2,15,18,20,25,35,38,52).…”

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confidence: 99%

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Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency

Koopman¹,

Visch²,

Verkaart³

et al. 2005

American Journal of Physiology-Cell Physiology

182

148

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Complex I (NADH:ubiquinone oxidoreductase) is the largest multisubunit assembly of the oxidative phosphorylation system, and its malfunction is associated with a wide variety of clinical syndromes ranging from highly progressive, often early lethal, encephalopathies to neurodegenerative disorders in adult life. The changes in mitochondrial structure and function that are at the basis of the clinical symptoms are poorly understood. Video-rate confocal microscopy of cells pulse-loaded with mitochondria-specific rhodamine 123 followed by automated analysis of form factor (combined measure of length and degree of branching), aspect ratio (measure of length), and number of revealed marked differences between primary cultures of skin fibroblasts from 13 patients with an isolated complex I deficiency. These differences were independent of the affected subunit, but plotting of the activity of complex I, normalized to that of complex IV, against the ratio of either form factor or aspect ratio to number revealed a linear relationship. Relatively small reductions in activity appeared to be associated with an increase in form factor and never with a decrease in number, whereas relatively large reductions occurred in association with a decrease in form factor and/or an increase in number. These results demonstrate that complex I activity and mitochondrial structure are tightly coupled in human isolated complex I deficiency. To further prove the relationship between aberrations in mitochondrial morphology and pathological condition, fibroblasts from two patients with a different mutation but a highly fragmented mitochondrial phenotype were fused. Full restoration of the mitochondrial network demonstrated that this change in mitochondrial morphology was indeed associated with human complex I deficiency.

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Section: Discussionsupporting

confidence: 85%

Section: Automated Analysis Of Mitochondrial Shape and Number In Humamentioning

confidence: 96%

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Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency

Koopman¹,

Visch²,

Verkaart³

et al. 2005

American Journal of Physiology-Cell Physiology

182

148

View full text Add to dashboard Cite

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“…Scale bar ϭ 100 nm. interconnected mitochondria in normal cultured fibroblasts (Handran et al, 1997) and in an immortalized human cancer cell line (HeLa cells; Rizzuto et al, 1998) A mitoplasmic reticulum can also be found in yeast (Fisk and Yaffe, 1997). One wonders, however, if this type of reticulum does not have a general occurrence.…”

Section: Close Association Of Er With Mitochondriamentioning

confidence: 96%

Membrane architecture of mitochondria in neurons of the central nervous system

Perkins¹,

Renken

Frey

et al. 2001

J of Neuroscience Research

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Electron tomography was used to help redefine the membrane architecture of mitochondria in neurons of the brain. Investigations were conducted on unexplored questions of structural homogeneity between mitochondria in the four intensely studied regions of the brain and in the functionally distinct neuronal sub-compartments. These mitochondria have the majority of cristae composed of both tubular and lamellar segments with the tubes arranged more peripherally and the lamellae more centrally located. Cristae that are entirely tubular were not commonly seen and those that are entirely lamellar were rare. It was determined that cristae connect through narrow, sometimes very long tubular regions to the peripheral surface of the inner membrane. A structurally distinct type of contact site was revealed in brain mitochondria, which we named the bridge contact site. These bridges may play a role in the structural integrity of the outer and inner membrane systems. It was found that the membrane architecture in the various brain regions and neuronal compartments was strikingly uniform, including consistently tubular crista junctions. The functional consequences of this junctional architecture are discussed in relation to the segregation of proteins between the inner boundary membrane and the cristae membranes, and in relation to the model of microcompartmentation of macromolecules inside cristae.

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“…Accordingly, it was demonstrated that mitochondria can control SOC in a numerous cell types and that the collapse of mitochondrial membrane potential, either by an uncoupler or an inhibitor of the respiratory chain, greatly reduces the SOC (Makowska et al, 2000). In an earlier study, Handran and collaborators failed to document either mitochondrial morphology alteration or intracellular Ca 2+ deregulation in COX-deficient human fibroblasts (Handran et al, 1997). This discrepancy between these results may be accounted on the partial recovery of COX enzyme activity in COX deficient fibroblasts.…”

Section: Calcium Deregulation In Oxphos Diseases Linked To Defects Inmentioning

confidence: 95%

Mitochondrial Calcium Signalling: Role in Oxidative Phosphorylation Diseases

Oulès¹,

Dolores²,

Chami³

2012

Bioenergetics

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Mitochondrial Morphology and Intracellular Calcium Homeostasis in Cytochrome Oxidase-Deficient Human Fibroblasts

Cited by 15 publications

References 38 publications

Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency

Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency

Membrane architecture of mitochondria in neurons of the central nervous system

Mitochondrial Calcium Signalling: Role in Oxidative Phosphorylation Diseases

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