Genetics of Apoptosis

6.

Mitochondria in apoptosis induction

Bruno Antonsson

1.

Introduction

Multicellular organisms are dependent on an ordered removal of unwanted and
damaged cells. This is ensured by apoptosis or programmed cell death. Apoptosis is
an energy (ATP)-requiring process that is conserved from low organisms such as the
roundworm C.elegans, where apoptosis was initially identified, up to mammals,
including man (Hengartner and Horvitz, 1994b). However, although apoptosis is
essential for normal development and for maintenance of a balanced tissue
homeostasis in adult animals, it is also involved in a wide range of diseases. Increased
apoptosis has been associated with stroke, myocardial infarction, reperfusion injury,
arteriosclerosis, heart failure, infertility, diabetes, AIDS, hepatitis, renal failure, and
neurodegenerative diseases such as multiple sclerosis (MS), amyotropic lateral
sclerosis (ALS), and Alzheimer’s, Huntington’s, and Parkinson’s diseases (Kuhlmann
et al., 1999; Kockx and Herman, 2000; Yaoita et al., 2000; Yuan and Yankner, 2000;
Chandra et al., 2001). However, impaired apoptosis is associated with various forms
of cancer and autoimmune diseases (Krammer, 2000).

2.

The mitochondria

The mitochondria are the power plants of the cells. Without the energy, in the form
of ATP, produced by mitochondrial respiration, cells cannot survive under normal
conditions. Mitochondria are complex, well-organized intracellular structures,
comprising an outer membrane (MOM), an inner membrane (MIM), an
intermembrane space, and cristae structures formed by the folding of the inner
membrane and the mitochondrial matrix on the inside of the inner membrane. The
biochemical composition of the inner and outer membranes, in terms of lipid and
protein composition, is different. The outer mitochondrial membrane is a fairly
permeable membrane allowing free passage of molecules with a molecular mass of
less than 1.5 kDa. The membrane contains two large channels or pores, the voltage-
dependent anion channel (VDAC) and the protein import channel, the translocase