Article

Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 09/2008; 1777(9):1092-7. DOI: 10.1016/j.bbabio.2008.05.001
Source: PubMed

ABSTRACT

The mitochondrial life cycle consists of frequent fusion and fission events. Ample experimental and clinical data demonstrate that inhibition of either fusion or fission results in deterioration of mitochondrial bioenergetics. While fusion may benefit mitochondrial function by allowing the spreading of metabolites, protein and DNA throughout the network, the functional benefit of fission is not as intuitive. Remarkably, studies that track individual mitochondria through fusion and fission found that the two events are paired and that fusion triggers fission. On average each mitochondrion would go though approximately 5 fusion:fission cycles every hour. Measurement of Deltapsi(m) during single fusion and fission events demonstrates that fission may yield uneven daughter mitochondria where the depolarized daughter is less likely to become involved in a subsequent fusion and is more likely to be targeted by autophagy. Based on these observations we propose a mechanism by which the integration of mitochondrial fusion, fission and autophagy forms a quality maintenance mechanism. According to this hypothesis pairs of fusion and fission allow for the reorganization and sequestration of damaged mitochondrial components into daughter mitochondria that are segregated from the networking pool and then becoming eliminated by autophagy.

Download full-text

Full-text

Available from: Gilad Twig
  • Source
    • "Another possible factor causing heterogeneity in mitochondrial content is the dynamics of mitochondrial biogenesis , which is characterized by continuous cycles of fusion and fission. However, these processes are fast compared to the cell-cycle period: on average, each mitochondrion undergoes around 5 fusion:fission cycles per hour[72], and this will likely promote a " steady " population of mitochondria inside the cell[72,73]. It is interesting to note that mitochondrial fusion and fission dynamics are regulated during the cell cycle[74], with mitochondrial fission enhanced during mitosis, which could facilitate passive and stochastic segregation of mitochondria to daughter cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gene expression activity is heterogeneous in a population of isogenic cells. Identifying the molecular basis of this variability will improve our understanding of phenomena like tumor resistance to drugs, virus infection, or cell fate choice. The complexity of the molecular steps and machines involved in transcription and translation could introduce sources of randomness at many levels, but a common constraint to most of these processes is its energy dependence. In eukaryotic cells, most of this energy is provided by mitochondria. A clonal population of cells may show a large variability in the number and functionality of mitochondria. Here, we discuss how differences in the mitochondrial content of each cell contribute to heterogeneity in gene products. Changes in the amount of mitochondria can also entail drastic alterations of a cell's gene expression program, which ultimately leads to phenotypic diversity. Also watch the Video Abstract.
    Full-text · Article · Dec 2015 · BioEssays
  • Source
    • "Ongoing fusion and fission of mitochondria is a prerequisite for the elimination of damaged mitochondria by mitophagy. After a fission event, daughter mitochondria frequently show different polarization states in terms of membrane potential (Twig et al. , 2008 ). It is not elucidated, though, whether fission specifically occurs at functionally impaired sites to separate these parts from the rest of the mitochondrion (Figure 4B). "

    Full-text · Dataset · Aug 2015
  • Source
    • "Defects in mitochondrial dynamics that result in respiratory chain impairment underlie Parkinson's disease (Kim et al. 2007; Twig et al. 2008; Westermann 2010; Amo et al. 2011). Mitophagy selectively removes a single deleterious mitochondrion (which is discussed later) (Westermann 2010), separating damaged from healthy mitochondria (Twig et al. 2008). Damaged/depolarized/reactive oxygen species (ROS) producing mitochondria are marked by externalized cardiolipin and surface ubiquitination, recognized by PINK1-Parkin and removed by mitophagy (Nunnari and Suomalainen 2012; Ji et al. 2012). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Traumatic brain injury (TBI) is still the leading cause of disability in young adults worldwide. The major mechanisms - diffuse axonal injury, cerebral contusion, ischemic neurological damage, and intracranial hematomas have all been shown to be associated with mitochondrial dysfunction in some form. Mitochondrial dysfunction in TBI patients is an active area of research, and attempts to manipulate neuronal/astrocytic metabolism to improve outcomes have been met with limited translational success. Previously, several preclinical and clinical studies on TBI induced mitochondrial dysfunction have focused on opening of the mitochondrial permeability transition pore (PTP), consequent neurodegeneration and attempts to mitigate this degeneration with cyclosporine A (CsA) or analogous drugs, and have been unsuccessful. Recent insights into normal mitochondrial dynamics and into diseases such as inherited mitochondrial neuropathies, sepsis and organ failure could provide novel opportunities to develop mitochondria-based neuroprotective treatments that could improve severe TBI outcomes. This review summarizes those aspects of mitochondrial dysfunction underlying TBI pathology with special attention to models of penetrating traumatic brain injury, an epidemic in modern American society.
    Full-text · Article · Oct 2014 · Journal of Bioenergetics
Show more