ARTICLE
Auteur(s) : V. Nollent, F. Bonté
LVMH Recherche
185, avenue du Verdun
45804 St Jean de Braye
<rdinfocom-mt@lvmh-pc.com>
The LVMH Recherche symposium 2005 on the topic of mitochondria
brought together, in Paris, more than 150 scientists. Leading
specialists from the USA, UK, Italy, Germany and France described
their latest discoveries and presented their most recent data.
This cellular organelle is at the heart of bioenergetics, tissue
homeostasis and aging, particular in the skin. It is thus most
important for the development of skincare products by the cosmetics
industry.
Mitochondria (mt) are multifunctional organelles derived from a
bacterial ancestor that established a symbiotic relationship with
eukaryotic cells early in the evolution of living things. Every
cell in the human body has hundreds or thousands of
energy-producing mitochondria. They are involved in a range of
cellular processes, including energy production, proliferation,
cell death and aging. They form a dynamic network that efficiently
delivers energy to all parts of the cell. Mitochondria can also
undergo fission or fusion, depending on the cell’s energy
requirements. The past few decades have seen the discovery of
diseases that specifically involve mitochondria, so that they are
now considered to be key players in aging, cellular homeostasis,
cancer and neurodegenerative disorders. These complex organelles
are also influenced by environmental factors and appear to be of
great importance for skin quality.
This 2005 LVMH Recherche symposium was dedicated to several
specific aspects of mitochondria around the themes : The
complexity of mitochondria and The mitochondria and the
environment.
Mitochondria are key elements for human life and harbour
proteins that can be released into the cytosol, where they govern
programmed cell death and are the guardians of cell
homeostasis.
Mitochondrial DNA comes only from the mother’s egg and can be used
to trace maternal ancestry without the complicating effects of
mixing genes from both parents. The mt genome is relatively small
and contains few genes. There is now good evidence that the
expression of mt genes can be modulated by nuclear genes and new
data indicate that there is cross talk between mt genes and those
of the nucleus (Pr P. Roubertoux, CNRS & Université de
Marseille, France). An accumulation of mutagenic oxidative
mitochondrial DNA lesions like 8-oxodeoxyguanine is involved in the
development of mitochondrial dysfunction in aging and in disorders
associated with aging. The unprotected mitochondrial genome is more
sensitive to reactive oxygen species than is the nuclear genome. An
age-dependent decline in mt DNA repair has been recently linked to
a decline in 8-oxoG DNA glycosidase activity (OGG1) and an
accumulation of AP-endonuclease (APE1) in mitochondria (Pr S.
Mitra, University of Texas, Galveston, USA).
Mitochondria are the main source of ATP, but they also play an
important role in calcium-dependent signal transmission,
thermogenesis, control of body weight, the urea cycle, production
of reactive oxygen species (ROS), apoptosis, and steroid hormone
synthesis. Respiration begins in the lungs but involves the cells
of all tissues. An adult at rest uses 36kg of ATP per day, all of
which is synthesized and used within the body. (Pr
I.E.Scheffler, University of California, San Diego, USA).
The mitochondrial respiratory cycle is based on the transfer of
electrons from NADH or succinate to molecular oxygen. This electron
transfer is accompanied by the release of protons from the
mitochondrial matrix into the intermembrane space. The resulting
electrochemical gradient generates a transmembrane current that is
often used as an indicator of cell viability or mitochondrial
function. Any break in the electron transport chain interferes with
ATP production and hence disrupts the cell’s energy supply.
Mitochondrial function diminishes with age, so that they tend to
provide insufficient energy production for optimal cell
function.
This could explain the changes that occur in skin cells during
aging. Aged mitochondria convert fuel to biological energy less
efficiently and produce more toxic oxygen species. If the only
electron acceptor available during the reduction of oxygen at the
cell surface is oxygen itself, the production of highly toxic
superoxide anions increases, leading to oxidative processes such as
lipid peroxidation. And the oxidation of lipids within the membrane
is the first step in a vicious cycle of reactions that amplifies
aging phenomena (Pr A. de Grey, University of Cambridge,
UK). This is particularly important for the skin. Oxidative
stress can also result in the breakdown of mitochondrial matrix
proteins and oxidized proteins are known to accumulate during
aging. The ATP-stimulated protease Lon or the enzyme aconitase, an
essential component of the Krebs cycle, become inactivated with
age, but the rate varies from one organ to another (Pr B.
Friguet, Université Paris 7, France). UV light and
environmental stress also influence the mitochondrial genome,
energy metabolism and the expression of skin fibroblast genes
(Pr J.Krutmann, IUF, Düsseldorf, Germany). The mitochondria
also regulate the response to stress and apoptosis. For example,
recent data indicate that basal epidermal skin cells are extremely
sensitive to stress, with dissipation of the mitochondrial
potential and activation of the protease caspase-8, indicating
activation of the extrinsic signalling pathway of death receptors.
A defect in the phosphorylation of P53 and a decrease in bax
underly the decreased apoptosis that occurs in skin cells with
aging (M. Dumas, LVMH Recherche, France). The longevity of
long-lived subjects such as centenarians may be due to specific
modulation of the apoptotic signal of p53 and the maintenance
of an efficient autophagic capacity for eliminating damaged
mitochondria (Pr S. Salvioli, University of Bologna, Italy).
The many laboratories that work on mitochondria and mtDNA
specialize in diverse fields, including medicine, botany and
cosmetology. Mitochondria play a role in many metabolic tasks and
functions, such as the production of reactive oxygen species and
stress. Thus the mitochondrion is a major actor in the regulation
of stress, cell homeostasis and longevity.
This LVMH Recherche symposium provided a powerful affirmation of
the importance of mitochondria as a leading topic in research on
the structure and function of the skin.
|
Printable version
Version PDF